Cancer Research and Treatment

Original Articles

Postoperative Radiotherapy May Improve Survival in Certain Patients with pN2 Non-Small Cell Lung Cancer Who Do Not Have Extranodal Extension: Seung Hyuck Jeon, Changhoon Song, Jae Hyun Jeon, Jin-Haeng Chung, Sukki Cho, Kwhanmien Kim, Sanghoon Jheon, Se Hyun Kim, Yu Jung Kim, Jae-Sung Kim; Received June 20, 2025 Accepted February 1, 2026 Published online February 3, 2026; DOI: https://doi.org/10.4143/crt.2025.644 [Epub ahead of print]

Abstract PDF: Purpose
The aim of this study was to identify subgroups of patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) who may benefit from postoperative radiotherapy (PORT). Particular attention was given to evaluating whether extranodal extension (ENE) influences the therapeutic efficacy of PORT.
Materials and Methods
A total of 231 patients with pN2 NSCLC who underwent surgical resection followed by adjuvant chemotherapy at a single institution were analyzed retrospectively. Propensity score matching was performed to compare treatment outcomes according to the receipt of PORT.
Results
Propensity score matching yielded 99 matched pairs of patients with no significant differences in clinical parameters. There were no significant differences in the overall survival (OS; p=0.112) and disease-free survival (DFS; p=0.286) between the PORT and no PORT groups. However, PORT significantly improved the locoregional recurrence (LRR)–free rate (p=0.011), whereas the distant metastasis–free rate was comparable between groups (p=0.646). In subgroup analyses, PORT was associated with improved OS in patients with 1-3 positive N2 lymph nodes (p=0.013) and with significantly improved DFS among patients without ENE (p=0.046) or lymphatic invasion (p=0.032).
Conclusion
Although PORT did not improve OS or DFS in the matched overall cohort, it significantly reduced LRR. Subgroup analyses suggested potential benefits in patients with limited nodal burden and in those without ENE or lymphatic invasion. These findings, however, should be interpreted cautiously given small subgroup sizes and inherent limitations of retrospective design.

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Biomarker Testing Practices for Non–Small Cell Lung Cancer: Survey Insights from South Korean Pathology Laboratories: Sehui Kim, Dajeong Kim, Lucia Kim, Wan-Seop Kim; Received September 29, 2025 Accepted January 28, 2026 Published online January 30, 2026; DOI: https://doi.org/10.4143/crt.2025.927 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Molecular biomarker testing is essential for lung cancer management and precision medicine. This study evaluated biomarker testing practices for non–small cell lung cancer (NSCLC) across pathology laboratories in South Korea.
Materials and Methods
A nationwide survey of 30 pathology laboratories assessed testing policies, biomarker adoption, testing platforms, next-generation sequencing (NGS) implementation, reporting practices, turnaround times (TATs), and perceived challenges.
Results
All institutions routinely performed biomarker testing; 20 (66.7%) employed reflex testing at least in part. Tissue was the primary specimen type, and cytology and liquid biopsy specimens were accepted by 90.0% and 46.7% of institutions, respectively. For non-squamous NSCLC, all institutions tested epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, and programmed cell death ligand 1 (PD-L1), with additional testing for BRAF (86.7%) and KRAS (80.0%); other actionable targets were rarely tested outside NGS. In squamous NSCLC, PD-L1 was routinely assessed, whereas other drivers were tested less frequently. All institutions performed tissue-based NGS using companion diagnostic (CDx) and/or non-CDx platforms, and liquid biopsy–based NGS was available in 46.7% of institutions. Median TATs were 2-3, 5, 9, 19, and 15 days for immunohistochemistry, polymerase chain reaction, fluorescence in situ hybridization, tissue-based NGS, and liquid biopsy–based NGS, respectively. Reported barriers included limited sample availability, workforce shortages, prolonged TATs, regulatory restrictions, and lack of standardization.
Conclusion
Biomarker testing is widely implemented in South Korea, with increasing integration of NGS. Despite alignment with international recommendations, systemic and policy reforms are needed to harmonize workflows, reduce variability, and optimize precision oncology.

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Real-World Efficacy and Safety of First-Line Chemo-immunotherapy in Extensive-Stage Small Cell Lung Cancer and Its Association with Molecular Subtype: Miran Han, Sehhoon Park, Se-Hoon Lee, Junkyu Kim, Jin-yong Kim, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn; Received September 3, 2025 Accepted November 4, 2025 Published online November 5, 2025; DOI: https://doi.org/10.4143/crt.2025.971 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Small cell lung cancer (SCLC) is an aggressive malignancy with poor outcomes. IMpower133 and CASPIAN established platinum–etoposide plus anti–programmed cell death-ligand 1 antibody as standard first-line therapy for extensive-stage SCLC (ESSCLC). Real-world data in Korean patients are scarce. We evaluated the effectiveness and safety of first-line chemo-immunotherapy in ES-SCLC and compared outcomes with pivotal trials.
Materials and Methods
We retrospectively reviewed patients diagnosed with ES-SCLC between 2018 and 2021. Overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT) were analyzed using Kaplan-Meier methods. Multivariate Cox regression identified prognostic factors. Objective response rate (ORR) was assessed by Response Evaluation Criteria in Solid Tumors ver. 1.1, and histological subtypes evaluated.
Results
Among 177 patients, median age was 66 years (range, 42 to 91 years), with 63.8% aged ≥ 65 years; most were male (92.7%) and Eastern Cooperative Oncology Group performance status 0-1 (91.5%). Smoking history was present in 80.8%. Baseline brain and liver metastases occurred in 27.7% and 26%. Median follow-up was 27.2 months (range, 3.9 to 43.2 months). ORR was 74.5% (95% confidence interval [CI], 67.1 to 81.1). Median OS, PFS, and TTNT were 12.4 (95% CI, 11.6 to 14.9), 5.3 (95% CI, 5.1 to 5.87), and 5.7 months (95% CI, 5.27 to 6.23). In 49 patients with brain metastases, ORR was 63.2%, with no difference in efficacy. Local therapy for brain metastases improved OS (hazard ratio, 0.42; p=0.012), while PFS was not different. Treatment-related adverse events occurred in 90%, primarily grade ≥ 2 cytopenias; the most common immune-related event was grade 1 rash.
Conclusion
In this real-world Korean cohort, first-line chemo-immunotherapy achieved outcomes comparable to pivotal trials, supporting its role as standard care for ES-SCLC in clinical practice.

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Preferential Sensitivity of the EGFR L858M/L861R Mutation to Second-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer: Chaelin Lee, Sheehyun Kim, Soyeon Kim, Taekeun Park, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Jeonghwan Youk; Received March 11, 2025 Accepted August 19, 2025 Published online August 20, 2025; DOI: https://doi.org/10.4143/crt.2025.279 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Non–small cell lung cancer (NSCLC) frequently harbors targetable epidermal growth factor receptor (EGFR) mutations. However, rare variants such as EGFR L858M or L861R remain poorly characterized. This study aimed to elucidate the oncogenic potential and EGFR tyrosine kinase inhibitors (TKIs) sensitivity of the EGFR L858M/L861R mutation to inform personalized treatment strategies.
Materials and Methods
Tumor samples from an NSCLC patient were analyzed using targeted panel sequencing and confirmed with the FoundationOne Liquid CDx assay. EGFR-mutant constructs, including L858M, L858R, L861R, L861Q, L858M/L861R, and L858R/L861Q, were generated and transduced into various cell lines. Cell viability, immunoblot, and soft agar colony formation assays were conducted to assess the oncogenicity and drug sensitivity, while computational protein modeling and docking simulations evaluated the drug-binding affinities of EGFR-TKIs.
Results
Ba/F3 cells expressing the EGFR L858M/L861R mutation exhibited robust interleukin-3–independent proliferation accompanied by markedly increased EGFR phosphorylation, while NIH-3T3 cells showed anchorage-independent colony formation. Compared to other mutations, cells expressing EGFR L858M/L861R mutation were less sensitive to first-generation EGFR-TKIs (gefitinib, erlotinib) and third-generation EGFR-TKIs (osimertinib, lazertinib), whereas second-generation EGFR-TKIs (afatinib, poziotinib) demonstrated potent inhibitory effects. Computational modeling revealed a narrower drug-binding efficiency of first-generation inhibitors.
Conclusion
The EGFR L858M/L861R mutation drives strong oncogenic signaling and exhibits preferential sensitivity to second-generation EGFR-TKIs. These findings underscore the importance of accurate molecular diagnosis for guiding effective, personalized therapeutic strategies in NSCLC.

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Real-World Outcomes and Subsequent Treatment Patterns in Patients with Advanced Non-Small Cell Lung Cancer and Atypical EGFR Mutations Receiving First-Line Osimertinib Monotherapy
Jorge J. Nieva, Xuejun Wang, Deborah Doroshow, Leslie Servidio, Miranda Cooper, Yan Kwan Lau, Pritesh S. Karia, Jacqulyne Robichaux
Oncology and Therapy.2026; 14(1): 225. CrossRef
Leitlinienentwicklung zur MRD-Diagnostik der AML als Blaupause für solide Tumoren
Michael Heuser, Claudia Wickenhauser, Leonie Oevel, Marcus Bauer
Die Pathologie.2026; 47(4): 273. CrossRef

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Lung and Thoracic cancer

Tracing Metastatic Evolutionary Patterns in Lung Adenocarcinoma: Prognostic Dissection Based on a Multi-state Model: Geewon Lee, Yang-Jin Kim, Insuk Sohn, Jong Hoon Kim, Ho Yun Lee; Cancer Res Treat. 2025;57(4):1019-1029. Published online January 24, 2025; DOI: https://doi.org/10.4143/crt.2024.700

Abstract PDF Supplementary Material PubReader ePub

Purpose
After surgery for lung adenocarcinoma, a patient may experience various states of recurrence, with multiple factors potentially influencing the transitions between these states. Our purpose was to investigate the effects of clinical and pathological factors on tumor recurrence, death, and prognosis across various metastasizing pathways.
Materials and Methods
Our study group included 335 patients with all demographic and pathologic data available who underwent surgical resection for lung adenocarcinoma for more than 10 years. The following states of disease were defined: initial state, operation (OP); three intermediate states of local recurrence (LR), metastasis (Meta), and concurrent LR with metastasis (LR+Meta); and a terminal state, death. We identified eight transitions representing various pathways of tumor progression. We employed a multi-state model (MSM) to separate the impacts of multiple prognostic factors on the transitions following surgery.
Results
After surgery, approximately half of patients experienced recurrence. Specifically, 142 (42.4%), 54 (16.1%), and seven (2.1%) patients developed Meta, LR+Meta, and LR, respectively. Clinical and pathological factors associated with the transitions were different. Impact of pathological lymph node remained a risk factor for both OP to Meta (λ02, p=0.001) and OP to LR+Meta (λ03, p=0.001).
Conclusion
Lung adenocarcinoma displays a broad spectrum of clinical scenarios even after curative surgery. Incidence, risk factors, and prognosis varied across different pathways of recurrence in lung adenocarcinoma patients. The greatest implication of this MSM is its ability to predict the timing and type of clinical intervention that will have the greatest impact on survival.

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A‐to‐I RNA Edited miR‐3167 Restrains Malignant Behaviors of Lung Adenocarcinoma by Influencing SSR2‐Meditated Hippo Signaling
Dawei Qian, Dongsheng Zha, Yuanyao Sang, Jiangquan Tao, Bufeng Zhuang, Youshuang Cheng
Molecular Carcinogenesis.2025; 64(9): 1552. CrossRef

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The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells: Songji Oh, Soyeon Kim, Bhumsuk Keam, Jeonghwan Youk, Tae Min Kim, Dong-Wan Kim, Miso Kim; Cancer Res Treat. 2025;57(4):1040-1050. Published online January 7, 2025; DOI: https://doi.org/10.4143/crt.2024.728

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study focused on combining irinotecan with poly(ADP-ribose) polymerase (PARP) inhibitors to explore the potential for novel combination therapeutics in small cell lung cancer (SCLC).
Materials and Methods
We selected 10 different SCLC cell lines with diverse mutational backgrounds in DNA damage response (DDR) pathway genes to evaluate the efficacy of the combination of three PARP inhibitors and irinotecan. After the cells were exposed to the drugs for 7 days, cell viability was measured, and a combination index was calculated. Apoptotic signaling was assessed via western blot, and DNA damage was evaluated using an alkaline comet assay.
Results
We assessed the synergistic effects of PARP inhibitors and irinotecan in in vitro SCLC models, which revealed increased sensitivity, particularly in cells harboring BRCA mutations. However, even in cells lacking mutations in DDR pathway genes, the combination of the two drugs exhibited a synergistic effect. When treated with 50 nM irinotecan, the IC₅₀ fold changes for PARP inhibitors were as follows: olaparib, 1,649±4,049; talazoparib, 25±34.21; venadaparib, 336±596.01. This combination enhanced apoptosis signaling and increased p-chk1 and p-p53 protein levels. Additionally, the treatment of PARP inhibitor with irinotecan increased DNA damage, as visualized by the alkaline comet assay.
Conclusion
This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients.

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Identifying potential binding sites for complex formation between Tyrosyl-DNA phosphodiesterase 1 and poly [ADP-ribose] polymerase 1
Sophia Wang, Aykut Üren, Purushottam B. Tiwari
Physical Chemistry Chemical Physics.2026; 28(23): 14017. CrossRef
Synthetic lethality in cancer: mechanism exploration and therapeutic applications
Pusong Zhao, Peng Wang, Tianqi Xu, Ligang Chen, Qingge Jia, Mingyang Li
Cell Communication and Signaling.2026;[Epub] CrossRef

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Upfront Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy in Elderly Patients with Brain Metastases from Non–Small Cell Lung Cancer: A Retrospective Analysis of a 10-Year Bi-institutional Experience: Myungsoo Kim, Jihye Cha, Hun Jung Kim, Woo Chul Kim, Jeongshim Lee; Cancer Res Treat. 2025;57(1):47-56. Published online July 3, 2024; DOI: https://doi.org/10.4143/crt.2024.223

Abstract PDF PubReader ePub

Purpose
Stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) are increasingly used as initial therapies for brain metastases (BM). We aimed to assess the outcomes of SRS/FSRT in patients aged ≥ 65 years who had 1-10 BM from non–small cell lung cancer (NSCLC).
Materials and Methods
We retrospectively reviewed 91 elderly NSCLC patients with 222 BM who were treated with SRS/FSRT at two institutions between 2010 and 2020. The primary endpoint was overall survival (OS) after SRS/FSRT. In addition, in-field local control (IFLC) within the treated field was evaluated. Statistical analysis was performed to identify the prognostic factors affecting OS and IFLC.
Results
During a median follow-up of 18 months, the median OS was 32 months. The 1- and 2-year survival rates were 69.8% and 56.1%, respectively. In multivariate analysis, the NSCLC-specific graded prognostic assessment (GPA) score (p=0.007) and administration of systemic therapy (p=0.039) were defined as prognosticators affecting OS. The median IFLC period was 31 months, and the 1- and 2-year IFLC rates were 75.9% and 57.6%, respectively. The total BM volume (p=0.042) significantly affected IFLC. No severe adverse events were reported after SRS/FSRT.
Conclusion
SRS/FSRT is an effective upfront treatment option for BM arising from NSCLC in elderly patients, with a good OS without severe side effects. Higher GPA score and active systemic treatment were associated with improved OS, indicating that elderly patients are significant candidates for SRS/FSRT.

Citations

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Prognostic factors, patterns of failure and re-irradiation in hypofractionated stereotactic radiotherapy-treated brain metastases from non-small cell lung cancer
Dayu Xu, Yechun Pang, Jinghan Qu, Jiuang Mao, Tiantian Guo, Shanshan Jiang, Yue Zhou, Li Chu, Xi Yang, Xiao Chu, Shengping Wang, Tong Tong, Zhengfei Zhu, Jianjiao Ni
Clinical and Translational Radiation Oncology.2025; 55: 101038. CrossRef
Prognostic Analysis of Lung Cancer With Brain Metastases in Elderly Patients: A Multicenter Retrospective Study
Anqi Li, Daqin Feng, Chang Liu, Chaojue Huang, Tang Li, Donggui Wei, Fangyi Wei, Muling Shen, Congzhi Qin, Shufang Deng, Hui Liang, Panlin Mo, Minhai Dong, Yongjia Yu, Lun Liang
AGING MEDICINE.2025; 8(6): 585. CrossRef

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Analytical and Clinical Validation of a Highly Sensitive NGS-Based ctDNA Assay with Real-World Concordance in Non–Small Cell Lung Cancer: Hanbaek Yi, Jeonghwan Youk, Yoojoo Lim, Hanseong Roh, Dongsoo Kyung, Hwang-Phill Kim, Duhee Bang, Bhumsuk Keam, Tae-Min Kim, Miso Kim, Dong-Wan Kim, Tae-You Kim; Cancer Res Treat. 2024;56(3):765-773. Published online January 8, 2024; DOI: https://doi.org/10.4143/crt.2023.1294

Abstract PDF Supplementary Material PubReader ePub

Purpose
There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay.
Materials and Methods
Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results.
Results
The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R²=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations.
Conclusion
The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

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Trastuzumab deruxtecan in non-breast solid tumors: Expanding indications, efficacy, and future directions
A. Ghidini, R. Bukovec, L. Roncari, L. Dottorini, F. Petrelli
Critical Reviews in Oncology/Hematology.2026; 220: 105158. CrossRef
Preoperative Circulating Tumor DNA Detection and Risk Stratification in Esophageal Squamous Cell Carcinoma
Tae Hee Hong, Jun-Gi Jeong, Seong Yong Park, Byung Jo Park, Dongsoo Kyung, Hwang-Phil Kim, Jingjun Zhu, Young Ho Yang, Ha Eun Kim, Chang Young Lee, Jin Gu Lee, Yeong Jeong Jeon, Junghee Lee, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Se-Hoon Lee, Dae Joo
JAMA Surgery.2026; 161(4): 370. CrossRef
Biological basis and clinical translation prospects of circulating cell‑free DNA in precision management of breast cancer (Review)
Li-Zhuang Fan, Ai-Lan Xu, Ya-Ru Xu, Luo Yang, Fang Yuan, Xin Nie
Oncology Letters.2026; 31(6): 1. CrossRef
Phase II study of trastuzumab-pkrb plus gedatolisib in patients with HER2-positive metastatic breast cancer who progressed after two or more HER2-directed therapies
J.W. Kim, Y.H. Park, S. Lee, H.K. Ahn, J. Bae, S. Park, H. Chae, J.H. Kim, K.-H. Lee, M.H. Kim, K.E. Lee, M.J. Kang, I.H. Park, Y.s. Chae, G.W. Lee, K.U. Park, E.M. Lee, J.H. Park, J.E. Kim, H.J. Kim, T.H. Kim, S.Y. Oh, S. Ko, J.H. Byun, J.Y. Ha, J.H. Kwo
ESMO Open.2026; 11(7): 107706. CrossRef
Reporting of molecular test results from cell-free DNA analyses: expert consensus recommendations from the 2023 European Liquid Biopsy Society ctDNA Workshop
Vincent D. de Jager, Patrizio Giacomini, Jennifer A. Fairley, Rodrigo A. Toledo, Simon J. Patton, Simon A. Joosse, Claudia Koch, Zandra C. Deans, Sofia Agelaki, Claus Lindbjerg Andersen, Daniel Andersson, Beatriz Bellosillo, Inger Riise Bergheim, Daan van
eBioMedicine.2025; 114: 105636. CrossRef
Improvement of the sensitivity of circulating tumor DNA-based liquid biopsy: current approaches and future perspectives
Ekaterina S. Kuligina, Grigoriy A. Yanus, Evgeny N. Imyanitov
Exploration of Targeted Anti-tumor Therapy.2025;[Epub] CrossRef
Next-generation sequencing impact on cancer care: applications, challenges, and future directions
Mariano Zalis, Gilson Gabriel Viana Veloso, Pedro Nazareth Aguiar Jr., Nathalia Gimenes, Marina Xavier Reis, Silvio Matsas, Carlos Gil Ferreira
Frontiers in Genetics.2024;[Epub] CrossRef
Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study
Shih-Chieh Chang, Yu-Feng Wei, Chung-Yu Chen, Yi-Chun Lai, Po-Wei Hu, Jui-Chi Hung, Cheng-Yu Chang
Molecular Diagnosis & Therapy.2024; 28(6): 803. CrossRef
Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
Journal of Hepatology.2024;[Epub] CrossRef

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Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non–Small Cell Lung Cancer: Bo-Guen Kim, Byeong-Ho Jeong, Goeun Park, Hong Kwan Kim, Young Mog Shim, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Jong Ho Cho; Cancer Res Treat. 2024;56(2):502-512. Published online December 4, 2023; DOI: https://doi.org/10.4143/crt.2023.840

Abstract PDF Supplementary Material PubReader ePub: Purpose
It is unclear whether performing endosonography first in non–small cell lung cancer (NSCLC) patients with radiological N1 (rN1) has any advantages over surgery without nodal staging. We aimed to compare surgery without endosonography to performing endosonography first in rN1 on the overall survival (OS) of patients with NSCLC.
Materials and Methods
This is a retrospective analysis of patients with rN1 NSCLC between 2013 and 2019. Patients were divided into ‘no endosonography’ and ‘endosonography first’ groups. We investigated the effect of nodal staging through endosonography on OS using propensity score matching (PSM) and multivariable Cox proportional hazard regression analysis.
Results
In the no endosonography group, pathologic N2 occurred in 23.0% of patients. In the endosonography first group, endosonographic N2 and N3 occurred in 8.6% and 1.6% of patients, respectively. Additionally, 51 patients were pathologic N2 among 249 patients who underwent surgery and mediastinal lymph node dissection (MLND) in endosonography first group. After PSM, the 5-year OSs were 68.1% and 70.6% in the no endosonography and endosonography first groups, respectively. However, the 5-year OS was 80.2% in the subgroup who underwent surgery and MLND of the endosonography first group. Moreover, in patients receiving surgical resection with MLND, the endosonography first group tended to have a better OS than the no endosonography group in adjusted analysis using various models.
Conclusion
In rN1 NSCLC, preoperative endosonography shows better OS than surgery without endosonography. For patients with rN1 NSCLC who are candidates for surgery, preoperative endosonography may help improve survival through patient selection.

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Tissue and Plasma-Based Highly Sensitive Blocker Displacement Amplicon Nanopore Sequencing for EGFR Mutations in Lung Cancer: Patinya Akkhasutthikun, Pornchai Kaewsapsak, Pattaraporn Nimsamer, Pavit Klomkliew, Suthida Visedthorn, Pragwalai Chanchaem, Chinachote Teerapakpinyo, Sunchai Payungporn, Sutima Luangdilok; Cancer Res Treat. 2024;56(2):455-463. Published online November 20, 2023; DOI: https://doi.org/10.4143/crt.2023.1108

Abstract PDF Supplementary Material PubReader ePub

Purpose
The epidermal growth factor receptor (EGFR) mutation is a widely prevalent oncogene driver in non–small cell lung cancer (NSCLC) in East Asia. The detection of EGFR mutations is a standard biomarker test performed routinely in patients with NSCLC for the selection of targeted therapy. Here, our objective was to develop a portable new technique for detecting EGFR (19Del, T790M, and L858R) mutations based on Nanopore sequencing.
Materials and Methods
The assay employed a blocker displacement amplification (BDA)–based polymerase chain reaction (PCR) technique combined with Nanopore sequencing to detect EGFR mutations. Mutant and wild-type EGFR clones were generated from DNA from H1650 (19Del heterozygous) and H1975 (T790M and L858R heterozygous) lung cancer cell lines. Then, they were mixed to assess the performance of this technique for detecting low variant allele frequencies (VAFs). Subsequently, formalin-fixed, paraffin-embedded (FFPE) tissue and cell-free DNA (cfDNA) from patients with NSCLC were used for clinical validation.
Results
The assay can detect low VAF at 0.5% mutant mixed in wild-type EGFR. Using FFPE DNA, the concordance rates of EGFR 19Del, T790M, and L858R mutations between our method and Cobas real-time PCR were 98.46%, 100%, and 100%, respectively. For cfDNA, the concordance rates of EGFR 19Del, T790M, and L858R mutations between our method and droplet digital PCR were 94.74%, 100%, and 100%, respectively.
Conclusion
The BDA amplicon Nanopore sequencing is a highly accurate and sensitive method for the detection of EGFR mutations in clinical specimens.

Citations

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Long-read sequencing for cancer liquid biopsy: advancing precision oncology
Grace Guzman, Analiz Rodriguez
Frontiers in Oncology.2026;[Epub] CrossRef
Decoding EGFR A289 Mutation in Glioblastoma: A Predictive Biomarker Framework and Targeted Therapeutic Insights
Xiaoxue Zhu, Haitao Fu, Xuejing Li, Hang Zhou, Zekai Li, Luyang Xie, Guilin Li
Journal of Molecular Neuroscience.2025;[Epub] CrossRef
Bullous Congenital Ichthyosiform Erythroderma with Tinea Capitis in Half-Siblings: Rare Phenomenon in Ichthyosis with Co-Existing Trichophyton rubrum Infection and Blocker Displacement Amplification for Mosaic Mutation Detection
Jipeng Liu, Yujuan Fu, Qihao Zhang, Qi Chen, Yuxiang Yang, Yi Xue, Yunqing Ren
Biomedicines.2025; 13(8): 2015. CrossRef
Cancer liquid biopsies by Oxford Nanopore Technologies sequencing of cell-free DNA: from basic research to clinical applications
Hua-Qi Si, Peng Wang, Fei Long, Wei Zhong, Yuan-Dong Meng, Yuan Rong, Xiang-Yu Meng, Fu-Bing Wang
Molecular Cancer.2024;[Epub] CrossRef

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The Real-World Outcome of First Line Atezolizumab in Extensive-Stage Small Cell Lung Cancer: A Multicenter Prospective Cohort Study: Myeong Geun Choi, Yeon Joo Kim, Jae Cheol Lee, Wonjun Ji, In-Jae Oh, Sung Yong Lee, Seong Hoon Yoon, Shin Yup Lee, Jeong Eun Lee, Eun Young Kim, Chang-Min Choi; Cancer Res Treat. 2024;56(2):422-429. Published online October 23, 2023; DOI: https://doi.org/10.4143/crt.2023.913

Abstract PDF Supplementary Material PubReader ePub

Purpose
The addition of immune checkpoint inhibitors to chemotherapy has improved survival outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC). However, their real-world effectiveness remains unknown. Therefore, we investigated the effectiveness of atezolizumab plus chemotherapy in ES-SCLC in actual clinical settings.
Materials and Methods
In this multicenter prospective cohort study, patients with ES-SCLC receiving or scheduled to receive atezolizumab in combination with etoposide and carboplatin were enrolled between June 2021 and August 2022. The primary outcomes were progression-free survival (PFS) and the 1-year overall survival (OS) rate.
Results
A total of 100 patients with ES-SCLC were enrolled from seven centers. Median age was 69 years, and 6% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2. The median PFS was 6.0 months, the 1-year OS rate was 62.2%, and the median OS was 13.5 months. An ECOG PS of 2-3 and progressive disease as the best response were poor prognostic factors for PFS, while an ECOG PS of 2-3 and brain metastasis were associated with poor prognosis for OS. In addition, consolidative thoracic radiotherapy was found to be an independent favorable prognostic factor for OS (hazard ratio, 0.336; p=0.021). Grade ≥ 3 treatment-related adverse events were observed in 7% of patients, with treatment-related deaths occurring in 2% of patients.
Conclusion
We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients, including in the elderly and those with poor ECOG PS. Additional consolidative thoracic radiotherapy may also benefit ES-SCLC patients.

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Real-World Treatment Patterns and Clinical Outcomes in Patients With Extensive-Stage Small Cell Lung Cancer Treated With First-Line Platinum-Based Chemotherapy and ≥ 2 Subsequent Lines of Therapy in the United States
Kamya Sankar, Sudhir Unni, Marian Eberl, Hoa Le, Tara Herrmann, Boris Gorsh, Mei Tang, Friso Coerts, Sajid Ahmed
Advances in Therapy.2026; 43(1): 214. CrossRef
Atezolizumab in the first-line treatment of small cell lung cancer: Toxicity and safety in real-world clinical practice
Ju. S. Mansurova, M. A. Lyadova, E. A. Denisova, E. S. Kuzmina, V. К. Lyadov
Meditsinskiy sovet = Medical Council.2026; (21): 20. CrossRef
Atezolizumab plus platinum-based chemotherapy and etoposide as first-line treatment for metastatic small cell lung cancer: a retrospective multicenter observational study
Laura Moñino Domínguez, Laura Amaro Álvarez, Alicia Aguado Paredes, Isabel María Carrión Madroñal
Farmacia Hospitalaria.2026;[Epub] CrossRef
Real-World Evidence of Atezolizumab Efficacy as Part of First-Line Treatment for Extensive-Stage SCLC in Bulgaria
Manoela Manova, Boryana Ivanova, Rositsa Krasteva, Nikolay Conev, Tanya Zlatanova, Jeliazko Arabadjiev, Natalia Chilingirova, Mila Petrova, Assen Dudov, Bozhil Robev, Velko Minchev, Ivan Tonev, Krassimir Koynov, Daniel Penchev, Todor Georgiev, Antoan Rang
Cancers.2026; 18(7): 1129. CrossRef
[Artículo traducido] Atezolizumab más quimioterapia con platino y etopósido como tratamiento de primera línea en cáncer de pulmón microcítico metastásico: estudio multicéntrico observacional retrospectivo
Laura Moñino Domínguez, Laura Amaro Álvarez, Alicia Aguado Paredes, Isabel María Carrión Madroñal
Farmacia Hospitalaria.2026;[Epub] CrossRef
First-Line Serplulimab in Extensive-Stage Small Cell Lung Cancer
Jingjing Liu, Liang Han, Lin Wu, Jun Chen, Hongmei Sun, Guilan Wen, Yinghua Ji, Jianhua Shi, Zhijie Pan, Jinsheng Shi, Xicheng Wang, Yuansong Bai, Yueyin Pan, Xuhong Min, Maksym Viguro, Xingya Li, Yanqiu Zhao, Junquan Yang, Tamta Makharadze, Ekaterine Ark
JAMA Oncology.2026;[Epub] CrossRef
Personalized tumor-loaded monocyte-derived dendritic cell vaccination in combination with atezolizumab as maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC): phase Ib-II VENEZOLUNG trial
Maria Gonzalez-Cao, Marta Sisteré-Oró, Teresa Moran, Noemi Reguart, Raquel Cabezon, Andres Aguilar Hernández, Ruth Roman, Miguel A Molina-Vila, Kürşat Birgin, Eva Domenjo-Vila, Gemma Piqué, Miquel Lozano, Paola Charry, Roxana Reyes, Irene Moya, Lluis Cire
Journal for ImmunoTherapy of Cancer.2026; 14(7): e015351. CrossRef
Multicenter retrospective study on the clinical profiles of patients with extensive-stage small-cell lung cancer who met the eligibility criteria for clinical trials
Tatsuya Yazaki, Kei Sonehara, Toshiharu Tsutsui, Shuhei Nozawa, Toshihiko Agatsuma, Manabu Yamamoto, Akemi Matsuo, Masanori Nakanishi, Tomoshige Chiaki, Akane Kato, Takashige Miyahara, Tsutomu Hachiya, Shintaro Kanda, Masayuki Hanaoka
Current Problems in Cancer.2026; 64: 101327. CrossRef
Significance of Platinum‐Based Chemotherapy With Programmed Death‐1 Blockade in Limited Disease Small Cell Lung Cancer: A Retrospective Study
Ayako Shiono, Hisao Imai, Kyoichi Kaira, Takanori Abe, Yuki Sato, Ken Yamamoto, Hiroki Watanabe, Yuko Tsuchiya‐Kawano, Akihiro Tamiya, Takashi Osaki, Noriko Yanagitani, Shigeru Tanzawa, Toshiyuki Sumi, Kohei Yoshimine, Yohei Matsui, Satoshi Endo, Kazuhiko
Thoracic Cancer.2025;[Epub] CrossRef
Impact of Treatment Duration in First-Line Atezolizumab Plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer: A Multicenter Real-World Retrospective Study
Mehmet Nuri Baser, Bilgin Demir, Gamze Serin Ozel, Gamze Gokoz Dogu, Serdar Karakaya, Mucahit Ugar, Naziye Ak, Ahmet Ozveren, Ufuk Camanlı, Olcun Umit Unal, Merve Turan, Esin Oktay
Medicina.2025; 61(7): 1230. CrossRef
Extended Follow‐Up Analysis of First‐Line Atezolizumab in Extensive‐Stage Small Cell Lung Cancer: A Real‐World Multicenter Prospective Cohort Study
Yechan Song, Myeong Geun Choi, Yeon Joo Kim, Jae Cheol Lee, Wonjun Ji, In‐Jae Oh, Sung Yong Lee, Seong Hoon Yoon, Shin Yup Lee, Jeong Eun Lee, Eun Young Kim, Ho Young Kim, Chang‐Min Choi
Thoracic Cancer.2025;[Epub] CrossRef

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Revolutionizing Non–Small Cell Lung Cancer Diagnosis: Ultra-High-Sensitive ctDNA Analysis for Detecting Hotspot Mutations with Long-term Stored Plasma: Ji-Young Lee, Seyeon Jeon, Ha Ra Jun, Chang Ohk Sung, Se Jin Jang, Chang-Min Choi, Sung-Min Chun; Cancer Res Treat. 2024;56(2):484-501. Published online October 23, 2023; DOI: https://doi.org/10.4143/crt.2023.712

Abstract PDF Supplementary Material PubReader ePub

Purpose
Circulating cell-free DNA (cfDNA) has great potential in clinical oncology. The prognostic and predictive values of cfDNA in non–small cell lung cancer (NSCLC) have been reported, with epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in tumor-derived cfDNAs acting as biomarkers during the early stages of tumor progression and recurrence. However, extremely low tumor-derived DNA rates hinder cfDNA application. We developed an ultra-high-sensitivity lung version 1 (ULV1) panel targeting BRAF, KRAS, and EGFR hotspot mutations using small amounts of cfDNA, allowing for semi-quantitative analysis with excellent limit-of-detection (0.05%).
Materials and Methods
Mutation analysis was performed on cfDNAs extracted from the plasma of 104 patients with NSCLC by using the ULV1 panel and targeted next-generation sequencing (CT-ULTRA), followed by comparison analysis of mutation patterns previously screened using matched tumor tissue DNA.
Results
The ULV1 panel demonstrated robust selective amplification of mutant alleles, enabling the detection of mutations with a high degree of analytical sensitivity (limit-of-detection, 0.025%-0.1%) and specificity (87.9%-100%). Applying ULV1 to NSCLC cfDNA revealed 51.1% (23/45) samples with EGFR mutations, increasing with tumor stage: 8.33% (stage I) to 78.26% (stage IV). Semi-quantitative analysis proved effective for low-mutation-fraction clinical samples. Comparative analysis with PANAMutyper EGFR exhibited substantial concordance (κ=0.84).
Conclusion
Good detection sensitivity (~80%) was observed despite the limited volume (1 mL) and long-term storage (12-50 months) of plasma used and is expected to increase with high cfDNA inputs. Thus, the ULV1 panel is a fast and cost-effective method for early diagnosis, treatment selection, and clinical follow-up of patients with NSCLC.

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Interlesional Heterogeneity of EGFR Mutations: A Systematic Review and Meta-analysis
Diana Ivonne Rodríguez Sánchez, Selin Asli Öztürk, Olga Maxouri, Stevie van der Mierden, Winnie Schats, Sajjad Rostami, Stephan Ursprung, Petur Snaebjornsson, Zuhir Bodalal, Regina Beets-Tan
Molecular Diagnosis & Therapy.2026; 30(2): 177. CrossRef
Emerging role of low-frequency somatic mutations in cancer relapse: from early detection to precision oncology
Eunsoo Kim, Gu Seob Roh, Seong Gyu Kwon
Frontiers in Oncology.2026;[Epub] CrossRef
The Role of ctDNA for Diagnosis and Histological Prediction in Early Stage Non-Small-Cell Lung Cancer: A Narrative Review
Carolina Sassorossi, Jessica Evangelista, Alessio Stefani, Marco Chiappetta, Antonella Martino, Annalisa Campanella, Elisa De Paolis, Dania Nachira, Marzia Del Re, Francesco Guerrera, Luca Boldrini, Andrea Urbani, Stefano Margaritora, Angelo Minucci, Emil
Diagnostics.2025; 15(7): 904. CrossRef
Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence
Tae-Kyung Robyn Yoo, Ji-Young Lee, Hwan Park, Whi-Kyung Cho, Seyeon Jeon, Ha Ra Jun, Sae Byul Lee, Il Yong Chung, Hee Jeong Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei-Hyun Ahn, Jae Ho Jeong, Jeong Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim
Scientific Reports.2024;[Epub] CrossRef

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Targeting CD73 to Overcomes Resistance to First-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer: Miso Kim, Soyeon Kim, Jeemin Yim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Dae Seog Heo; Cancer Res Treat. 2023;55(4):1134-1143. Published online May 23, 2023; DOI: https://doi.org/10.4143/crt.2023.311

Abstract PDF Supplementary Material PubReader ePub

Purpose
In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs.
Materials and Methods
We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed.
Results
High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI.
Conclusion
High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.

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Profiling of Extracellular Vesicles of Non‐Small Cell Lung Cancer Reveals Proteins Associated With Osimertinib Resistance
Albano Cáceres‐Verschae, Petra Hååg, Sofia Joelsson, Per Hydbring, Bo Franzén, Ákos Végvári, Inger Johanne Z. Eide, Nupur Agarwal, Siddharth Sourabh Sahu, Fredrik Stridfeldt, Luigi De Petris, Apurba Dev, Simon Ekman, Odd Terje Brustugun, Rolf Lewensohn, K
Journal of Extracellular Vesicles.2026;[Epub] CrossRef
CD73 expression as a resistance mechanism in advanced EGFR-mutated non-small cell lung cancer
Inger Johanne Zwicky Eide, Anne Pernille Harlem Dyrbekk, Ina Bisha, Thomas Haberichter, Sotirios Lakis, Jessica Chan, Arthur Lewis, Philip Martin, Zachary A. Cooper, Odd Terje Brustugun
Frontiers in Oncology.2026;[Epub] CrossRef
Research Progress of CD73 Inhibitors in Lung Cancer Immunotherapy
菀凌张
World Journal of Cancer Research.2026; 16(03): 176. CrossRef
Simultaneous blockade of the CD73/EGFR axis inhibits tumor growth
Keivan Ardeshiri, Hadi Hassannia, Ghasem Ghalamfarsa, Hanieh Jafary, Farhad Jadidi
IUBMB Life.2025;[Epub] CrossRef
Exploring the Expression of CD73 in Lung Adenocarcinoma with EGFR Genomic Alterations
Elodie Long-Mira, Christophe Bontoux, Guylène Rignol, Véronique Hofman, Sandra Lassalle, Jonathan Benzaquen, Jacques Boutros, Salomé Lalvée-Moret, Katia Zahaf, Virginie Lespinet-Fabre, Olivier Bordone, Sophia Maistre, Christelle Bonnetaud, Charlotte Cohen
Cancers.2025; 17(6): 1034. CrossRef
Assessing the impact of CD73 inhibition on overcoming anti-EGFR resistance in glioma cells
LUIZ FERNANDO LOPES SILVA, JULIETE NATHALI SCHOLL, AUGUSTO FERREIRA WEBER, CAMILA KEHL DIAS, PAULINE RAFAELA PIZZATO, VINíCIUS PIERDONá LIMA, JEAN SÉVIGNY, ANA MARIA OLIVEIRA BATTASTINI, FABRÍCIO FIGUEIRÓ
Oncology Research.2025; 33(4): 951. CrossRef
CD39 and CD73: biological functions, diseases and therapy
Jie Shen, Bin Liao, Li Gong, Sha Li, Juan Zhao, Huiyao Yang, Yi Gong, Yongsheng Li
Molecular Biomedicine.2025;[Epub] CrossRef
Comprehensive pan-cancer analysis of CD73: Explore its association with prognosis and tumor immune microenvironment
Chen Chen, Sasa Liu, Yanfen Ma
Heliyon.2024; 10(22): e40329. CrossRef

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Expanded Access Program Pralsetinib in Advanced Non–Small Cell Lung Cancer with Rearranged during Transfection (RET) Gene Rearrangement: Youngkyung Jeon, Hyun Ae Jung, Sehhoon Park, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Se-Hoon Lee; Cancer Res Treat. 2023;55(4):1144-1151. Published online May 22, 2023; DOI: https://doi.org/10.4143/crt.2023.403

Abstract PDF PubReader ePub

Purpose
Rearranged during transfection (RET) gene rearrangement is a well-known driver event in non–small cell lung cancer (NSCLC). Pralsetinib is a selective inhibitor of RET kinase and has shown efficacy in oncogenic RET-altered tumors. This study evaluated the efficacy and safety of expanded access program (EAP) use of pralsetinib in pretreated, advanced NSCLC patients with RET rearrangement.
Materials and Methods
Patients who received pralsetinib as part of the EAP at Samsung Medical Center were evaluated through a retrospective chart review. The primary endpoint was overall response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1 guidelines. Secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and safety profiles.
Results
Between April 2020 and September 2021, 23 of 27 patients were enrolled in the EAP study. Two patients who were not analyzed due to brain metastasis and two patients whose expected survival was within 1 month were excluded from the analysis. After a median follow-up period of 15.6 months (95% confidence interval [CI], 10.0 to 21.2), ORR was 56.5%, the median PFS was 12.1 months (95% CI, 3.3 to 20.9), and the 12-month OS rate was 69.6%. The most frequent treatment-related adverse events (TRAEs) were edema (43.5%) and pneumonitis (39.1%). A total of 8.7% of patients experienced extra-pulmonary tuberculosis. TRAEs with a common grade of three or worse were neutropenia (43.5%) and anemia (34.8%). Dose reduction was required in nine patients (39.1%).
Conclusion
Pralsetinib presents a clinical benefit when used in patients with RET-rearranged NSCLC, consistent with a pivotal study.

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Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC
Francesca Lucibello, Valérie Gounant, Mihaela Aldea, Michaël Duruisseaux, Maurice Perol, Christos Chouaid, Jaafar Bennouna, Vincent Fallet, Aldo Renault, Florian Guisier, Etienne Giroux-Leprieur, Marie Wislez, Anne-Claire Toffart, Julien Mazieres, Clémenc
JTO Clinical and Research Reports.2025; 6(1): 100743. CrossRef
Real-world FAERS safety analysis of Pralsetinib
Dongdong Zhang, Yixin Sun, Ying Cai, Peiji Zeng, Yue Wang, Ming Cai, Chengfu Cai
Scientific Reports.2025;[Epub] CrossRef
Clinical evidence and adverse event management update of patients with RET- rearranged advanced non-small-cell lung cancer (NSCLC) treated with pralsetinib
Giuseppe Lo Russo, Paolo Bironzo, Chiara Bennati, Laura Bonanno, Annamaria Catino, Giulio Metro, Iacopo Petrini, Marco Russano, Antonio Passaro
Critical Reviews in Oncology/Hematology.2024; 194: 104243. CrossRef
RET Fusion Testing in Patients With NSCLC: The RETING Study
Esther Conde, Susana Hernandez, Jose Luis Rodriguez Carrillo, Rebeca Martinez, Marta Alonso, Daniel Curto, Beatriz Jimenez, Alejandra Caminoa, Amparo Benito, Pilar Garrido, Sergi Clave, Edurne Arriola, Isabel Esteban-Rodriguez, Javier De Castro, Irene San
JTO Clinical and Research Reports.2024; 5(4): 100653. CrossRef
Efficacy and safety of pralsetinib in patients with RET fusion positive non–small cell lung cancer: An observational real world study
Dehua Liao, Minghui Long, Jiwen Zhang, Xingyu Wei, Fei Li, Ting Yan, Desong Yang
Lung Cancer.2024; 196: 107936. CrossRef

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Sublobar Resection versus Stereotactic Body Radiation Therapy for Clinical Stage I Non–Small Cell Lung Cancer: A Study Using Data from the Korean Nationwide Lung Cancer Registry: Jeonghee Yun, Jong Ho Cho, Tae Hee Hong, Kyungmi Yang, Yong Chan Ahn, Hong Kwan Kim, Korean Association for Lung Cancer, Korea Central Cancer Registry; Cancer Res Treat. 2023;55(4):1171-1180. Published online April 17, 2023; DOI: https://doi.org/10.4143/crt.2022.1581

Abstract PDF Supplementary Material PubReader ePub

Purpose
Stereotactic body radiotherapy (SBRT) had been increasingly recognized as a favorable alternative to surgical resection in patients with high risk for surgery. This study compared survival outcomes between sublobar resection (SLR) and SBRT for clinical stage I non–small cell lung cancer (NSCLC).
Materials and Methods
Data were obtained from the Korean Association of Lung Cancer Registry, a sampled nationwide database. This study retrospectively reviewed 382 patients with clinical stage I NSCLC who underwent curative SLR or SBRT from 2014 to 2016.
Results
Of the patients, 43 and 339 underwent SBRT and SLR, respectively. Patients in the SBRT group were older and had worse pulmonary function. The 3-year overall survival (OS) rate was significantly better in the SLR group compared with the SBRT group (86.6% vs. 57%, log-rank p < 0.001). However, after adjusting for age, sex, tumor size, pulmonary function, histology, smoking history, and adjuvant therapy, treatment modality was not an independent prognostic factor for survival (hazard ratio, 0.99; 95% confidence interval, 0.43 to 2.77; p=0.974). We performed subgroup analysis in the following high-risk populations: patients who were older than 75 years; patients who were older than 70 years and had diffusing capacity of lung for carbon monoxide ≤ 80%. In each subgroup, there were no differences in OS and recurrence-free survival between patients who underwent SLR and those who received SBRT.
Conclusion
In our study, there were no significant differences in terms of survival or recurrence between SBRT and SLR in medically compromised stage I NSCLC patients. Our findings suggest that SBRT could be considered as a potential treatment option for selected patients.

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Real-world Decision-making Process for Stereotactic Body Radiotherapy Versus Minimally Invasive Surgery in Early-stage Lung Cancer Patients
Stijn Vanstraelen, Kay See Tan, Prasad S. Adusumilli, Manjit S. Bains, Matthew J. Bott, Robert J. Downey, Daniel R. Gomez, Katherine D. Gray, James Huang, James M. Isbell, Daniela Molena, Bernard J. Park, Andreas Rimner, Valerie W. Rusch, Narek Shaverdian
Annals of Surgery.2026; 283(5): 807. CrossRef
Sublobar resection, stereotactic body radiotherapy, and thermal ablation for early-stage non-small cell lung cancer: a systematic review and meta-analysis
Shahar Adar, Alexandra Ádám, Tamara Balogh, Mátyás Rédei, Karen Krisztina Fazekas, Mátyás Paczkó, Nina Galdzytska, Marie Anne Engh, András Bibok, Gábor Zoltán Duray, Péter Hegyi, Dénes Balázs Horváthy
Lung Cancer.2026; 217: 109467. CrossRef
The limits of pooled evidence in early-stage NSCLC: are we comparing treatments or patients?
Peter S.N. van Rossum, Famke L. Schneiders, Suresh Senan
Lung Cancer.2026; : 109555. CrossRef
Surgery Versus Stereotactic Body Radiotherapy for Early-Stage Non-small Cell Lung Cancer (NSCLC): A Comprehensive Review of Survival and Local Control Outcomes
Abdulrahman Bin Sumaida, Nandan M Shanbhag, Nadeem Pervez, Khalifa AlKaabi, Khalid Balaraj
Cureus.2025;[Epub] CrossRef
Surgery for all patients with T1N0 non-small cell lung cancer?
Claudia Pouypoudat, Sébastien Thureau, Nicolas Giraud, Yaniss Belaroussi, Étienne Martin
Cancer/Radiothérapie.2025; 29(5-6): 104683. CrossRef

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A Randomized Phase II Study of Irinotecan Plus Cisplatin with or without Simvastatin in Ever-Smokers with Extended Disease Small Cell Lung Cancer: Youngjoo Lee, Soo-Hyun Lee, Geon Kook Lee, Eun Jin Lim, Ji-Youn Han; Cancer Res Treat. 2023;55(3):885-893. Published online March 20, 2023; DOI: https://doi.org/10.4143/crt.2023.283

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)–small cell lung cancer (SCLC).
Materials and Methods
This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible. Patients were randomized to receive irinotecan plus cisplatin alone or with simvastatin (40 mg once daily orally) for a maximum of six cycles. Primary endpoint was the the 1-year survival rate.
Results
Between September 16, 2011, and September 9, 2021, 125 patients were randomly assigned to the simvastatin (n=62) or control (n=63) groups. The median smoking pack year was 40 years. There was no significant difference in the 1-year survival rate between the simvastatin and control groups (53.2% vs. 58.7%, p=0.535). The median progression-free survival and overall survival between the simvastatin arm vs. the control groups were 6.3 months vs. 6.4 months (p=0.686), and 14.4 months vs. 15.2 months, respectively (p=0.749). The incidence of grade 3-4 adverse events was 62.9% in the simvastatin group and 61.9% in the control group. In the exploratory analysis of lipid profiles, patients with hypertriglyceridemia had significantly higher 1-year survival rates than those with normal triglyceride levels (80.0% vs. 52.7%, p=0.046).
Conclusion
Addition of simvastatin to chemotherapy provided no survival benefit in ever-smokers with ED-SCLC. Hypertriglyceridemia may be associated with better prognosis in these patient population.

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Lipid Metabolic Reprogramming in Lung Cancer: Mechanisms and Therapeutic Targets in the Tumor Microenvironment
Shan Wang, Jing Yu
International Journal of Cancer.2026; 159(7): 1616. CrossRef
РОЛЬ СТАТИНОВ В ПРОТИВООПУХОЛЕВОЙ ТЕРАПИИ НА СОВРЕМЕННОМ ЭТАПЕ У ПАЦИЕНТОВ ПОЖИЛОГО И СТАРЧЕСКОГО ВОЗРАСТА
И.Б. Зуева, Ю.В. Ким, Н.С. Березин, Н.Г. Лукьянов, Н.А. Березина, М.А. Черкашин
Успехи геронтологии.2026; 39(1): 91. CrossRef
Cholesterol confers resistance to Apatinib-mediated ferroptosis in gastric cancer
Zhiwei Li, Chenxin Liu, Minghao Wang, Riqing Wei, Ru Li, Kaihua Huang, Huayuan Liang, Guoxin Li, Liying Zhao
Cell & Bioscience.2025;[Epub] CrossRef
Statins in the context of precision cancer medicine: important factors to consider
Francisco Alejandro Lagunas-Rangel
Medical Oncology.2025;[Epub] CrossRef
Beyond cardiovascular health: The pharmacotherapeutic potential of statins in oncology
Alaa Abdelhamid, Dima Nasrallah, Esraa Ahmed, Amirhossein Sahebkar, Ali H. Eid
Seminars in Cancer Biology.2025; 117: 1. CrossRef
Cardiovascular/anti‐inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta‐analysis of randomized trials
David J. Benjamin, Alyson Haslam, Vinay Prasad
Cancer Medicine.2024;[Epub] CrossRef
Repurposing simvastatin in cancer treatment: an updated review on pharmacological and nanotechnological aspects
Nargis Ara, Abdul Hafeez, Shom Prakash Kushwaha
Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(10): 7377. CrossRef
Strategies to Target Chemoradiotherapy Resistance in Small Cell Lung Cancer
Tony Yu, Benjamin H. Lok
Cancers.2024; 16(20): 3438. CrossRef
β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers
Pedro Gabriel Senger Braga, Janaína da Silva Vieira, Aline Rachel Bezerra Gurgel, Patricia Chakur Brum
Frontiers in Pharmacology.2024;[Epub] CrossRef
Statins—From Fungi to Pharmacy
Anna Sadowska, Patryk Osiński, Alicja Roztocka, Karolina Kaczmarz-Chojnacka, Ewa Zapora, Diana Sawicka, Halina Car
International Journal of Molecular Sciences.2023; 25(1): 466. CrossRef

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Efficacy of Prophylactic Cranial Irradiation According to the Risk of Extracranial Recurrence in Limited-Stage Small Cell Lung Cancer: Tae Hoon Lee, Joo-Hyun Chung, Hong-Gyun Wu, Suzy Kim, Joo Ho Lee, Bhumsuk Keam, Jin-Soo Kim, Ki Hwan Kim, Byoung Hyuck Kim, Hak Jae Kim; Cancer Res Treat. 2023;55(3):875-884. Published online February 24, 2023; DOI: https://doi.org/10.4143/crt.2022.1583

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for “early brain metastasis”, which occurs before extracranial recurrence (ECR), and “late brain metastasis”, which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC).
Materials and Methods
We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors.
Results
The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026).
Conclusion
PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.

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Efficacy evaluation of prophylactic cranial irradiation for limited stage small‑cell lung cancer in the magnetic resonance imaging era: A meta‑analysis
Lihua Shao, Yumei Dong, Meiqiao Jiang, Haixia Song, Yuexiao Qi, Liyun Guo, Jinhui Tian, Shihong Wei
Oncology Letters.2025;[Epub] CrossRef

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EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-Mutated NSCLC: A Prospective, Randomized, Exploratory Study: Weiguang Gu, Hua Zhang, Yiyu Lu, Minjing Li, Shuang Yang, Jianmiao Liang, Zhijian Ye, Zhihua Li, Minhong He, Xiaoliang Shi, Fei Wang, Dong You, Weiquan Gu, Weineng Feng; Cancer Res Treat. 2023;55(3):841-850. Published online February 13, 2023; DOI: https://doi.org/10.4143/crt.2022.1438

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations.
Materials and Methods
This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.
Results
The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.
Conclusion
EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

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Optimal Definition of Oligometastasis Showing Survival Benefits of Local Therapies during Tyrosine Kinase Inhibitor Treatment: Yoon Jung Jang, Dong-gon Hyun, Wonjun Ji, Chang-Min Choi, Shinkyo Yoon, Dae Ho Lee, Sang-We Kim, Jae Cheol Lee; Cancer Res Treat. 2023;55(2):468-478. Published online November 28, 2022; DOI: https://doi.org/10.4143/crt.2022.1342

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to investigate the feasibility of four criteria on oligometastasis (OM) concerning clear survival benefits of local therapy (LT) during tyrosine kinase inhibitor (TKI) treatment in non–small cell lung cancer (NSCLC).
Materials and Methods
This single-center, retrospective study included patients with advanced NSCLC who received LT because of OM during TKI treatment at Asan Medical Center from January 2011 to December 2020. At the application of LT OM was classified according to four criteria: TNM, European Organization for Research and Treatment of Cancer Lung Cancer Group (EORTC-LCG), National Comprehensive Network (NCCN), and ORGAN. We compared survival outcomes between patients with and without OM.
Results
The median overall survival of the 117 patients included in the analysis was 70.8 months (95% confidence interval [CI], 56.6 to 85.1). The patients with OM meeting all four criteria (hazard ratio [HR] with 95% CI of TNM criteria 0.24 with 0.10-0.57; p=0.001, EORTC-LCG criteria 0.34 with 0.17-0.67; p=0.002, NCCN criteria 0.41 with 0.20-0.86; p=0.018 and ORGAN criteria 0.33 with 0.18-0.60; p < 0.001) had significantly longer survival compared with patients who did not after adjusting for confounding factors. Furthermore, increasing the number of extra-thoracic metastatic organs to two or more were independent predictive factors for worse survival outcomes (2 organs: HR, 3.51; 95% CI, 1.01 to 12.14; p=0.048; 3 organs: HR, 4.31; 95% CI, 0.94 to 19.73; p=0.060; 4 organs: HR, 24.47; 95% CI, 5.08 to 117.80; p < 0.001).
Conclusion
Patients with OM defined by all four criteria showed prognostic benefits from LT during TKI therapy.

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The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study: Seong Yong Park, Samina Park, Geun Dong Lee, Hong Kwan Kim, Sehoon Choi, Hyeong Ryul Kim, Yong-Hee Kim, Dong Kwan Kim, Seung-Il Park, Tae Hee Hong, Yong Soo Choi, Jhingook Kim, Jong Ho Cho, Young Mog Shim, Jae Ill Zo, Kwon Joong Na, In Kyu Park, Chang Hyun Kang, Young-Tae Kim, Byung Jo Park, Chang Young Lee, Jin Gu Lee, Dae Joon Kim, Hyo Chae Paik; Cancer Res Treat. 2023;55(1):94-102. Published online June 9, 2022; DOI: https://doi.org/10.4143/crt.2022.290

Abstract PDF Supplementary Material PubReader ePub

Purpose
This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery.
Materials and Methods
The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded.
Results
The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS.
Conclusion
Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

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Review Article

Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer: Joel Rivera-Concepcion, Dipesh Uprety, Alex A. Adjei; Cancer Res Treat. 2022;54(2):315-329. Published online February 18, 2022; DOI: https://doi.org/10.4143/crt.2022.078

Abstract PDF PubReader ePub

Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there has been a significant change in the management of patients with oncogene-addicted advanced-stage NSCLC. Increasing amounts of identifiable oncogene drivers have led to the development of molecularly targeted drugs. Undoubtedly, the future of thoracic oncology is shifting toward increased molecular testing and the use of targeted therapies. For the most part, these novel drugs have proven to be safe and effective. As with all great innovations, targeted therapies pose unique challenges. Drug toxicities, resistance, access, and costs are some of the expected obstacles that will need to be addressed. This review highlights some of the major challenges in the use of targeted therapies in NSCLC and provides guidance for the future strategies.

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Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies
Ricardo Teixo, Ana Salomé Pires, Eurico Pereira, Beatriz Serambeque, Inês Alexandra Marques, Mafalda Laranjo, Slavko Mojsilović, Roberto Gramignoli, Peter Ponsaerts, Andreina Schoeberlein, Maria Filomena Botelho
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Survival benefit of thermal ablation therapy for patients with stage II-III non-small cell lung cancer: A propensity-matched analysis
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Molecular targeted therapy for anticancer treatment
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Transcriptomic FHITlow/pHER2high signature as a predictive factor of outcome and immunotherapy response in non-small cell lung cancer
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CIGB-300 Anticancer Peptide Differentially Interacts with CK2 Subunits and Regulates Specific Signaling Mediators in a Highly Sensitive Large Cell Lung Carcinoma Cell Model
George V. Pérez, Mauro Rosales, Ailyn C. Ramón, Arielis Rodríguez-Ulloa, Vladimir Besada, Luis J. González, Daylen Aguilar, Dania Vázquez-Blomquist, Viviana Falcón, Evelin Caballero, Paulo C. Carvalho, Rodrigo Soares Caldeira, Ke Yang, Yasser Perera, Silv
Biomedicines.2022; 11(1): 43. CrossRef

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Original Articles

Lung and Thoracic cancer

Assessment of Anti-tumor Efficacy of Osimertinib in Non-Small Cell Lung Cancer Patients by Liquid Biopsy Using Bronchoalveolar Lavage Fluid, Plasma, or Pleural Effusion: Yeon Joo Kim, Won Jun Ji, Jae-Cheol Lee, Sung-Min Chun, Chang-Min Choi; Cancer Res Treat. 2022;54(4):985-995. Published online January 17, 2022; DOI: https://doi.org/10.4143/crt.2021.857

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was to evaluate anti-tumor efficacy of osimertinib in patients positive for acquired epidermal growth factor receptor (EGFR) T790M mutation in liquid biopsy using plasma, bronchoalveolar lavage fluid (BALF) or bronchial washing fluid (BWF), and pleural effusion.
Materials and Methods
Among patients benefited from previous EGFR‒tyrosine kinase inhibitor treatment followed by treatment failure, patients in whom T790M mutations are detected in at least one of the samples including tumor tissues, BALF/BWF, plasma, and pleural effusion were enrolled. T790M mutation was detected by extracting cell free DNA from liquid biopsy samples, using PANA Mutyper. Objective response rate (ORR) and progression-free survival (PFS) with osimertinib treatment were evaluated.
Results
Between January 2018 and December 2019, 63 patients were enrolled and received osimertinib. Mean age was 63 years, and 38 (60.3%) were female. Twenty-six patients had T790M mutation in both liquid and tissue samples (group A), 19 patients had only in tissue biopsy samples (group B), and 18 patients had T790M mutation only in liquid biopsy samples (group C). ORR in overall population was 63.5%, and was 61.5% in group A, 68.4% in group B, and 61.1% in group C, respectively. Median PFS in overall patients was 15.6 months (95% confidence interval, 10.7 to 24.2). There was no significant difference in ORR or PFS between groups.
Conclusion
Osimertinib showed favorable efficacy in lung cancer patients with acquired resistance to prior EGFR-TKI therapies, who screened positive for harboring T790M mutation detected from cell free DNA extracted from plasma, BALF/BWF, and pleural effusion.

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Cardiovascular adverse events in non-small cell lung cancer patients receiving osimertinib therapy: a systematic review and meta-analysis
Wei-He Liu, Yun-Jiu Cheng, Jin Kang, Jian Chen, Zhen-Jie An, Ting-Hui Li, Ning Tan, Wen-Zhao Zhong, Yi-Long Wu, Lei Jiang
Lung Cancer.2026; 217: 109413. CrossRef
Repeated rebiopsy for detection of EGFR T790M mutation in patients with advanced-stage lung adenocarcinoma: Associated factors and treatment outcomes of Osimertinib
Taeyun Kim, Junsu Choe, Sun Hye Shin, Byeong-Ho Jeong, Kyungjong Lee, Hojoong Kim, Se-Hoon Lee, Sang-Won Um, Hamidreza Montazeri Aliabadi
PLOS ONE.2024; 19(9): e0310079. CrossRef
Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?
Yi-Ze Li, Sheng-Nan Kong, Yun-Peng Liu, Yue Yang, Hong-Mei Zhang
Journal of Clinical Medicine.2023; 12(4): 1438. CrossRef
Usefulness of bronchial washing fluid for detection of EGFR mutations in non-small cell lung cancer
Woo Kyung Ryu, Seung Hyun Yong, Sang Hoon Lee, Hye Ran Gwon, Hye Ryun Kim, Min Hee Hong, Go Eun Oh, Sehee Jung, Chi Young Kim, Yoon Soo Chang, Eun Young Kim
Lung Cancer.2023; 186: 107390. CrossRef

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A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer: Eo Jin Kim, Yong-Hee Cho, Dong Ha Kim, Dae-Hyun Ko, Eun-Ju Do, Sang-Yeob Kim, Yong Man Kim, Jae Seob Jung, Yoonmi Kang, Wonjun Ji, Myeong Geun Choi, Jae Cheol Lee, Jin Kyung Rho, Chang-Min Choi; Cancer Res Treat. 2022;54(4):1005-1016. Published online December 3, 2021; DOI: https://doi.org/10.4143/crt.2021.986

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.
Materials and Methods
Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×10⁹ or 4×10⁹ cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life.
Results
Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×10⁹ cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001).
Conclusion
Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

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Fan Yang, Yihang Gong, Xiaofang Zheng, Beibei Ni, Jianxi Lu, Xiaoyan Chen, Jintao Cheng, Panlong Li, Cong Du, Yunhao Chen, Yingcai Zhang, Shuhong Yi, Guoying Wang, Qi Zhang, Yang Yang, Wenjie Chen
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Jie Ma, Jingjing Yue, Yangyang Li, Yutong Li, Hongbo Dong, Fang Fang, Weihua Xiao
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Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells
Jaya Lakshmi Thangaraj, Michael Coffey, Edith Lopez, Dan S. Kaufman
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Raj Kumar, Romi Gupta
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NK cell activity and methylated HOXA9 ctDNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors
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Xin Chen, Lei Jiang, Xuesong Liu
Frontiers in Immunology.2022;[Epub] CrossRef

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The Value of the Illness-Death Model for Predicting Outcomes in Patients with Non–Small Cell Lung Cancer: Kum Ju Chae, Hyemi Choi, Won Gi Jeong, Jinheum Kim; Cancer Res Treat. 2022;54(4):996-1004. Published online November 19, 2021; DOI: https://doi.org/10.4143/crt.2021.902

Abstract PDF Supplementary Material PubReader ePub

Purpose
The illness-death model (IDM) is a comprehensive approach to evaluate the relationship between relapse and death. This study aimed to illustrate the value of the IDM for identifying risk factors and evaluating predictive probabilities for relapse and death in patients with non–small cell lung cancer (NSCLC) in comparison with the disease-free survival (DFS) model.
Materials and Methods
We retrospectively analyzed 612 NSCLC patients who underwent a curative operation. Using the IDM, the risk factors and predictive probabilities for relapse, death without relapse, and death after relapse were simultaneously evaluated and compared to those obtained from a DFS model.
Results
The IDM provided more detailed risk factors according to the patient’s disease course, including relapse, death without relapse, and death after relapse, in patients with resected lung cancer. In the IDM, history of malignancy (other than lung cancer) was related to relapse and smoking history was associated with death without relapse; both were indistinguishable in the DFS model. In addition, the IDM was able to evaluate the predictive probability and risk factors for death after relapse; this information could not be obtained from the DFS model.
Conclusion
Compared to the DFS model, we found that the IDM provides more comprehensive information on transitions between states and disease stages and provides deeper insights with respect to understanding the disease process among lung cancer patients.

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Variable Selection for Illness‐Death Processes Under Dual Observation Schemes
Xianwei Li, Liqun Diao, Richard J. Cook
Statistics in Medicine.2026;[Epub] CrossRef
Risk prediction for ALS using semi-competing risk models with applications to the ALS Natural History Consortium dataset
Andres Arguedas, David Schneck, Erjia Cui, Annette Xenopoulos-Oddsson, Ximena Arcila-Londono, Christian Lunetta, James Wymer, Nicholas Olney, Kelly Gwathmey, Senda Ajroud-Driss, Ghazala Hayat, Terry Heiman-Patterson, Federica Cerri, Christina Fournier, Jo
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Population-based epidemiological projections of rheumatoid arthritis in Germany until 2040
J Wang, S Vordenbäumen, M Schneider, R Brinks
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A population-based projection of psoriatic arthritis in Germany until 2050: analysis of national statutory health insurance data of 65 million German population
Jiancong Wang, Sabrina Tulka, Stephanie Knippschild, Matthias Schneider, Jörg H. W. Distler, Xenofon Baraliakos, Ralph Brinks, Philipp Sewerin
Rheumatology International.2023; 43(11): 2037. CrossRef
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Wen Qin, Ping Wang, CuiMin Ding, Fei Peng
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Lung cancer mortality and associated predictors: systematic review using 32 scientific research findings
Lijalem Melie Tesfaw, Zelalem G. Dessie, Haile Mekonnen Fenta
Frontiers in Oncology.2023;[Epub] CrossRef

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Integrin αvβ3 Induces HSP90 Inhibitor Resistance via FAK Activation in KRAS-Mutant Non-Small Cell Lung Cancer: Shinkyo Yoon, Hannah Yang, Hyun-Min Ryu, Eunjin Lee, Yujin Jo, Seyoung Seo, Deokhoon Kim, Chang Hoon Lee, Wanlim Kim, Kyung Hae Jung, Sook Ryun Park, Eun Kyung Choi, Sang-We Kim, Kang-Seo Park, Dae Ho Lee; Cancer Res Treat. 2022;54(3):767-781. Published online September 30, 2021; DOI: https://doi.org/10.4143/crt.2021.651

Abstract PDF Supplementary Material PubReader ePub

Purpose
Heat shock protein-90 (HSP90) remains an important cancer target because of its involvement in multiple oncogenic protein pathways and biologic processes. Although many HSP90 inhibitors have been tested in the treatment of KRAS-mutant non–small cell lung cancer (NSCLC), most, including AUY922, have failed due to toxic effects and resistance generation, even though a modest efficacy has been observed for these drugs in clinical trials. In our present study, we investigated the novel mechanism of resistance to AUY922 to explore possible avenues of overcoming and want to provide some insights that may assist with the future development of successful next-generation HSP90 inhibitors.
Materials and Methods
We established two AUY922-resistant KRAS-mutated NSCLC cells and conducted RNA sequencing to identify novel resistance biomarker.
Results
We identified novel two resistance biomarkers. We observed that both integrin Av (ITGAv) and β3 (ITGB3) induce AUY922-resistance via focal adhesion kinase (FAK) activation, as well as an epithelial-mesenchymal transition, in both in vitro and in vivo xenograft model. mRNAs of both ITGAv and ITGB3 were also found to be elevated in a patient who had shown acquired resistance in a clinical trial of AUY922. ITGAv was induced by miR-142 downregulation, and ITGB3 was increased by miR-150 downregulation during the development of AUY922-resistance. Therefore, miR-150 and miR-142 overexpression effectively inhibited ITGAvB3-dependent FAK activation, restoring sensitivity to AUY922.
Conclusion
The synergistic co-targeting of FAK and HSP90 attenuated the growth of ITGAvB3-induced AUY922-resistant KRAS-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome acquired AUY922-resistance in KRAS-mutant NSCLC.

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Adaptive Feedback Signaling Through the FAK/SRC Pathway Promotes KRAS G12C Inhibitor Resistance
Hibiki Udagawa, Yuji Shibata, Monique B. Nilsson, Kazuya Nishii, Jacqulyne P. Robichaux, Ana Galan-Cobo, Junqin He, Alissa Poteete, Yu Qian, David Molkentine, Xiaoxing Yu, Qian Huang, Marcelo V. Negrao, John V. Heymach
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Triiodothyronine promotes the proliferation and chemoresistance of cholangiocarcinoma cells via HIF-1α/Glut1-stimulated glycolysis
Dihua Huang, Feng Xu, Luohang Xu, Zekai Tang, Yanxin Hu, Jiandong Li, Jianhua Yu
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2025; 1871(5): 167814. CrossRef
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Yoshinobu Kariya, Michiru Nishita
International Journal of Molecular Sciences.2025; 26(7): 3143. CrossRef
Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in EGFR‐Mutated Lung Cancer Cells Resistant to Osimertinib
Yu‐Ting Kang, Hui‐Yi Chang, Ya‐Chu Hsieh, Chia‐Hsuan Chou, I‐Lun Hsin, Jiunn‐Liang Ko
Environmental Toxicology.2024; 39(12): 5238. CrossRef
Junctional adhesion molecular 3 (JAM3) is a novel tumor suppressor and improves the prognosis in breast cancer brain metastases via the TGF-β/Smad signal pathway
Kaitao Zhu, Shiwei Li, Hongru Yao, Jilong Hei, WenGuo Jiang, Tracey Martin, Shanyi Zhang
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Cancer and Metastasis Reviews.2023; 42(1): 217. CrossRef

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miR-4487 Enhances Gefitinib-Mediated Ubiquitination and Autophagic Degradation of EGFR in Non-Small Cell Lung Cancer Cells by Targeting USP37: Mi Seong Kim, So Hui Kim, Sei Hoon Yang, Min Seuk Kim; Cancer Res Treat. 2022;54(2):445-457. Published online August 3, 2021; DOI: https://doi.org/10.4143/crt.2021.622

Abstract PDF PubReader ePub

Purpose
With the identification of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) cells, EGFR–tyrosine kinase inhibitors (TKIs) are being used widely as the first-line of treatment in NSCLC. These inhibitors block auto-phosphorylation of activated EGFR by competing with ATP binding and mediate EGFR degradation independent of exogenous epidermal growth factor, which is associated with the mutation variants of EGFR. However, the precise mechanisms underlying the TKI-mediated EGFR degradation are still unclear.
Materials and Methods
To examine the physiological roles of miR-4487 and ubiquitin-specific peptidase 37 (USP37) in gefitinib-mediated EGFR degradation in NSCLC cells, multiple NSCLC cell lines were applied. The level of EGFR expression, apoptosis marker and autophagic flux were determined by western blot. Expression level of miR-4487 and cell cycle arrest was analyzed by TaqMan assay and flow cytometry respectively.
Results
We found that gefitinib mediates EGFR degradation under normal culture conditions, and is dependent on autophagic flux and the mutation variants of EGFR. Gefitinib reduced expression levels of USP37, which mediated EGFR degradation similar to gefitinib. Our results also showed a gefitinib-mediated increase in endogenous miR-4487 level and presented evidence for the direct targeting of USP37 by miR-4487, resulting in the sequential enhancement of ubiquitination, autophagy, and EGFR degradation. Thus, the depletion of USP37 and overexpression of miR-4487 led to an increase in gefitinib-mediated apoptotic cell death.
Conclusion
These data suggest that miR-4487 is a potential target for treating NSCLC, and miR-4487/USP37-regulated EGFR degradation is a determinant for developing gefitinib resistance.

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Identification of Raptor and GLI1 as USP37 substrates highlight its context-specific function in medulloblastoma cells
Ashutosh Singh, Donghang Cheng, Amanda R. Haltom, Yanwen Yang, Tara Dobson, Rashieda Hatcher, Veena Rajaram, Vidya Gopalakrishnan
Oncogene.2026; 45(4): 521. CrossRef
The ubiquitination–autophagy axis in cancer therapy resistance: mechanistic insights and therapeutic opportunities
Hengrui Zhang, Hanxi Yan, Yulin Liu, Anqi Zeng, Linjiang Song
Frontiers in Pharmacology.2026;[Epub] CrossRef
USP37 facilitates hepatocellular carcinoma progression by deubiquitinating RAF1 and activating ERK1/2 signaling
Yuming Wang, Ruidong Ding, Yilin Wang, Xiangheng Cai, Jijun Shan
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Deubiquitination of epidermal growth factor receptor by ubiquitin-specific peptidase 54 enhances drug sensitivity to gefitinib in gefitinib-resistant non-small cell lung cancer cells
Mi Seong Kim, Min Seuk Kim, Chien-Feng Li
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Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non–Small Cell Lung Cancer: Chaelin Lee, Miso Kim, Dong-Wan Kim, Tae Min Kim, Soyeon Kim, Sun-Wha Im, Yoon Kyung Jeon, Bhumsuk Keam, Ja-Lok Ku, Dae Seog Heo; Cancer Res Treat. 2022;54(1):140-149. Published online May 3, 2021; DOI: https://doi.org/10.4143/crt.2021.385

Abstract PDF Supplementary Material PubReader ePub

Purpose
Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs.
Materials and Methods
We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDD^WT), EGFR-KDD domain 1 T790M (EGFR-KDD^D1T), EGFR-KDD domain 2 T790M (EGFR-KDD^D2T), and EGFR-KDD both domain T790M (EGFR-KDD^BDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening.
Results
In cell viability assays, SNU-4784 cells and EGFR-KDD^WT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDD^T790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDD^BDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDD^T/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs.
Conclusion
Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDD^T790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

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Acquired Resistance to Afatinib Mediated by EGFR T790M in Lung Adenocarcinoma Patients Harboring EGFR-KDD: A Case Report and Literature Review
Qian Liu, Lu Lv, Guanchao Pang, Pingli Wang
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Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors
Tomohiro Kondo, Osamu Kikuchi, Yoshihiro Yamamoto, Tomohiko Sunami, Yafeng Wang, Keita Fukuyama, Tomoki Saito, Hideto Nakahara, Sachiko Minamiguchi, Masashi Kanai, Atsushi Sueyoshi, Manabu Muto
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Ran Wang, Wei Ruan, Dang Fan, Li Long, Han Zhang, Min Li, Shan Xu, Linxiao Wang
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Shuangru Chen, Liting Zhang, Jun Wang, Jiayao Lu, Ye Chen, Mingzhu Ling
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Erlotinib

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Lung cancer

Active Treatment Improves Overall Survival in Extremely Older Non–Small Cell Lung Cancer Patients: A Multicenter Retrospective Cohort Study: Su Yeon Lee, Yoon-Ki Hong, Wonjun Ji, Jae Cheol Lee, Chang Min Choi, Korean Association for Lung Cancer, Korea Central Cancer Registry; Cancer Res Treat. 2021;53(1):104-111. Published online October 5, 2020; DOI: https://doi.org/10.4143/crt.2020.894

Abstract PDF Supplementary Material PubReader ePub

Purpose
As the aging of society progresses, the proportion of extremely older lung cancer patients has also increased; However, studies of these patients with non–small cell lung cancer are limited. Therefore, we investigated the initial treatment modalities and survival outcomes for patients aged 80 years or over.
Materials and Methods
We included a multicenter retrospective cohort from the Korean Association for Lung Cancer Registry, which surveys 10% of the newly diagnosed lung cancer patients across 52 hospitals in Korea. We analyzed and compared the 2014–2016 data of the non–small cell lung cancer patients aged ≥ 80 years and those aged < 80 years.
Results
Of the 6,576 patients reviewed, 780 patients were aged ≥ 80 years, and 5,796 patients were aged < 80 years. In the patients aged ≥ 80 years, surgery and radiation therapy resulted in longer patient survival among those with a resectable tumor (stage I–II) than the best supportive care (median survival, not reached [surgery] vs. 32.2 months [radiation therapy] vs. 11.43 months [best supportive care]). The duration of survival in patients with advanced-stage (IV) lung cancers was higher after chemotherapy than after the best supportive care (median survival, 8.63 months vs. 2.5 months). Patients with stage IV adenocarcinoma who received targeted therapy had better survival than those who did not (median survival, 9.0 months vs. 4.3 months).
Conclusion
Even in extremely older patients, active treatments, such as surgery, radiation therapy, and chemotherapy, can result in better survival outcomes than the best supportive care.

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Changes in Cancer Care for Patients Aged 80 and Above: A Cohort Study from Samsung Comprehensive Cancer Center in South Korea
Seung Tae Kim, Danbee Kang, Seok Jin Kim, Jun Ho Lee, Hong Kwan Kim, Yong Beom Cho, Yong Han Paik, Seok Won Kim, Byong Chang Jeong, Ho Jun Seol, Man Ki Chung, Kyu Taek Lee, Kihyun Kim, Sung-wook Seo, Jeong-Won Lee, Hee Chul Park, Dong Wook Shin, Juhee Cho
Cancers.2025; 17(12): 2017. CrossRef
The delayed cancer treatment and economic inequality in Korea: results of common cancers by the time-to-surgery
Noorhee Son, Woo-Ri Lee, Dong-Woo Choi, Kyu-Tae Han
Epidemiology and Health.2025; 47: e2025056. CrossRef
ADENOCARCINOMA PULMONAR - ASPECTOS EPIDEMIOLÓGICOS, FISIOPATOLÓGICOS E TERAPÊUTICOS
Marcelo Vinicius Pereira Silva, Elizeu Augusto de Freitas Junior, Allan Martins de Oliveira, Elaine Timm, Mariana Brito Siqueira, Mônica Stefany Martelli, Elielson Mendonça de Oliveira, Victor Cavalcante Machado, Igor Vinicius Barbino Ferrari, Pamella Hag
Revista Contemporânea.2024; 4(5): e4464. CrossRef
Association between clinical outcomes and local treatment in stage IV non‐small cell lung cancer patients with single extrathoracic metastasis
Jeong Uk Lim, Hye Seon Kang, Ah Young Shin, Chang Dong Yeo, Chan Kwon Park, Sang Haak Lee, Seung Joon Kim
Thoracic Cancer.2022; 13(9): 1349. CrossRef
Characteristics and clinical outcomes of patients with nonsmoking small cell lung cancer in Korea
Hye Seon Kang, Jung Uk Lim, Chang Dong Yeo, Chan Kwon Park, Sang Haak Lee, Seung Joon Kim, Ho Cheol Kim, Chang Min Choi, Chi Young Jung, Deog Gon Cho, Jae Hyun Jeon, Jeong Eun Lee, Jin Seok Ahn, Yeongdae Kim, Yoo-Duk Choi, Yang-Gun Suh, Jung-Eun Kim, Youn
BMC Pulmonary Medicine.2022;[Epub] CrossRef

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A Phase II Trial of Osimertinib as the First-Line Treatment of Non–Small Cell Lung Cancer Harboring Activating EGFR Mutations in Circulating Tumor DNA: LiquidLung-O-Cohort 1: Cheol-Kyu Park, Hyun-Ju Cho, Yoo-Duk Choi, In-Jae Oh, Young-Chul Kim; Cancer Res Treat. 2021;53(1):93-103. Published online September 21, 2020; DOI: https://doi.org/10.4143/crt.2020.459

Abstract PDF Supplementary Material PubReader ePub

Purpose
Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for both EGFR-activating and T790M resistant mutation. The treatment efficacy of osimertinib was assessed in previously untreated patients with metastatic non–small cell lung carcinoma (NSCLC) harboring activating EGFR mutations in circulating tumor DNA (ctDNA) as well as tumor DNA.
Materials and Methods
Patients with activating EGFR mutations in their tumor DNA underwent screening with ctDNA analysis using Mutyper and Cobas v2 assays. Enrolled subjects received osimertinib 80 mg, once daily. Primary endpoint was objective response rate (ORR) and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety.
Results
Among 39 screened patients, 29 were ctDNA positive for activating EGFR mutations and 19 were enrolled (ex19del, n=11; L858R/L861Q, n=7; G719A, n=1). Median age was 70 and most patients had brain metastases (15/19, 79%). ctDNA test sensitivity for activating EGFR mutations was 74% using both methods and 62% (Mutyper) or 64% (Cobas v2) for individual methods. ORR was 68% (13/19), median PFS was 11.1 months (95% confidence interval [CI], 0.0 to 26.7), and median DoR was 17.6 months (95% CI, 3.5 to 31.7). ORR and median PFS were significantly superior with ex19del (91%; 21.9 months; 95% CI, 5.5 to 38.3) than with L858R/L861Q (43%; 5.1 months; 95% CI, 2.3 to 7.9). One patient discontinued the drug because of drug-related interstitial pneumonitis.
Conclusion
Osimertinib had favorable efficacy in the first-line treatment of metastatic NSCLC harboring activating EGFR mutations in ctDNA as well as tumor DNA.

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Osimertinib for Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Current Evidence
Xiumei Tang, Yanmei Chen, Yuan Zhu, Yuan Liu, Weimin Li, Wenzhao Wang, Zhoufeng Wang
Clinical Medicine Insights: Oncology.2026;[Epub] CrossRef
Osimertinib in EGFR-mutated non-small cell lung cancer: a comprehensive narrative review of clinical evidence
Xiumei Tang, Yuan Zhu, Jiayi Yan, Haoying Wu, Yanmei Chen, Yuan Liu, Huairong Tang, Wenzhao Wang, Zhoufeng Wang
Journal of Translational Genetics and Genomics.2026; 10(2): 228. CrossRef
Impact of Variant Allele Frequency (VAF) Levels on Clinical Efficacy of Osimertinib in Patients with Metastatic NSCLC
Abed Agbarya, Kamel Mhameed, Arina Soklakova, Haitam Nasrallah, Mahmoud Abu Amna, Sabri El-Saied, Mohammad Sheikh-Ahmad, Walid Shalata
Medical Sciences.2026; 14(2): 233. CrossRef
Comparison Between EGFR-TKI Efficacy in Early-Stage Non-small Cell Lung Cancer and Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis
Bingxue Wang, Yang Yao, Zhangxuan Chen, Ranpu Wu, Jiajie Sun, Xinjing Li, Xuanhao Xu, Yunxiao Si, Hongbing Liu
Lung.2026;[Epub] CrossRef
Circulating tumor DNA to monitor treatment response in solid tumors and advance precision oncology
Alexandra Bartolomucci, Monyse Nobrega, Tadhg Ferrier, Kyle Dickinson, Nivedita Kaorey, Amélie Nadeau, Alberto Castillo, Julia V. Burnier
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Mara B. Antonoff, Carl M. Gay
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Valentina Favorito, Ilaria Ricciotti, Andrea De Giglio, Laura Fabbri, Renata Seminerio, Alessandro Di Federico, Eleonora Gariazzo, Silvia Costabile, Giulio Metro
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Juan Carlos Restrepo, Darly Martínez Guevara, Andrés Pareja López, John Fernando Montenegro Palacios, Yamil Liscano
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ctDNA SNORD3F Hypermethylation is a Prognostic Indicator in EGFR-TKI-Treated Advanced Non-Small Cell Lung Cancer
Bin Liu, Bingtian Zhao, Yan Yin, Yan Jiang, Xue Feng, Lei Wang, Liang Zhai, Guangxin Liu, Dongsheng Shi, Jianwen Qin
Cancer Management and Research.2024; Volume 16: 1405. CrossRef
Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?
Yi-Ze Li, Sheng-Nan Kong, Yun-Peng Liu, Yue Yang, Hong-Mei Zhang
Journal of Clinical Medicine.2023; 12(4): 1438. CrossRef
Effect of Osimertinib on CTCs and ctDNA in EGFR Mutant Non-Small Cell Lung Cancer Patients: The Prognostic Relevance of Liquid Biopsy
Galatea Kallergi, Emmanouil Kontopodis, Aliki Ntzifa, Núria Jordana-Ariza, Niki Karachaliou, Evangelia Pantazaka, Haris A. Charalambous, Amanda Psyrri, Emily Tsaroucha, Ioannis Boukovinas, Anna Koumarianou, Dora Hatzidaki, Evi Lianidou, Vassilis Georgouli
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Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer: Junghoon Shin, Jin-Haeng Chung, Se Hyun Kim, Kyu Sang Lee, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jeong-Ok Lee, Jin-Won Kim, Yu-Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong-Seok Lee; Cancer Res Treat. 2019;51(3):1086-1097. Published online November 5, 2018; DOI: https://doi.org/10.4143/crt.2018.537

Abstract PDF PubReader ePub

Purpose
Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications.
Materials and Methods
We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival.
Results
The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival.
Conclusion
Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

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Journal of Hematology & Oncology.2022;[Epub] CrossRef
PD‐1 blockade using pembrolizumab in adolescent and young adult patients with advanced bone and soft tissue sarcoma
Tahlia Scheinberg, Anna Lomax, Martin Tattersall, David Thomas, Geoff McCowage, Michael Sullivan, Rooshdiya Karim, Peter P. Luk, Annabelle Mahar, Fiona Bonar, Vivek A. Bhadri
Cancer Reports.2021;[Epub] CrossRef
PD‐L1 versus tumor mutation burden: Which is the better immunotherapy biomarker in advanced non‐small cell lung cancer?
Aoran Dong, Yiming Zhao, Zhihua Li, Hai Hu
The Journal of Gene Medicine.2021;[Epub] CrossRef
Biomarkers predicting the response to chemotherapy and the prognosis in patients with esophageal squamous cell carcinoma
Seiya Inoue, Takahiro Yoshida, Takeshi Nishino, Masakazu Goto, Mariko Aoyama, Naoya Kawakita, Yota Yamamoto, Furukita Yoshihito, Hiromitsu Takizawa, Akira Tangoku
General Thoracic and Cardiovascular Surgery.2021; 69(3): 525. CrossRef
Patient-Reported Outcomes with Durvalumab by PD-L1 Expression and Prior Chemoradiotherapy-Related Variables in Unresectable Stage III Non-Small-Cell Lung Cancer
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Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer
S. Sugawara, J.-S. Lee, J.-H. Kang, H.R. Kim, N. Inui, T. Hida, K.H. Lee, T. Yoshida, H. Tanaka, C.-T. Yang, M. Nishio, Y. Ohe, T. Tamura, N. Yamamoto, C.-J. Yu, H. Akamatsu, Y. Namba, N. Sumiyoshi, K. Nakagawa
Annals of Oncology.2021; 32(9): 1137. CrossRef
Temporal evolution of programmed death-ligand 1 expression in patients with non-small cell lung cancer
Chang Hyun Nam, Jaemoon Koh, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Doo Hyun Chung, Dae Seog Heo
The Korean Journal of Internal Medicine.2021; 36(4): 975. CrossRef
Methylseleninic acid overcomes programmed death‐ligand 1‐mediated resistance of prostate cancer and lung cancer
Wenli Hu, Yurong Ma, Chong Zhao, Shutao Yin, Hongbo Hu
Molecular Carcinogenesis.2021; 60(11): 746. CrossRef
Immunological Status of Bladder Cancer Patients Based on Urine Leukocyte Composition at Radical Cystectomy
Elisabet Cantó, Óscar Rodríguez Faba, Carlos Zamora, Maria Mulet, Maria Soledad Garcia-Cuerva, Ana Palomino, Georgia Anguera, Alberto Breda, Pablo Maroto, Sílvia Vidal
Biomedicines.2021; 9(9): 1125. CrossRef
Ex vivo expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells through different receptor-ligand interactions
Daun Jung, Young Seok Baek, In Jee Lee, Ki Yeon Kim, Heejoo Jang, Sohyun Hwang, Jieun Jung, Yong-wha Moon, Kyung-Soon Park, Yong-Soo Choi, Hee Jung An
Journal of Experimental & Clinical Cancer Research.2021;[Epub] CrossRef
Prognostic significance of T‐cell–inflamed gene expression profile and PD‐L1 expression in patients with esophageal cancer
Torben Steiniche, Sun Young Rha, Hyun Cheol Chung, Jeanette Baehr Georgsen, Morten Ladekarl, Marianne Nordsmark, Marie Louise Jespersen, Hyo Song Kim, Hyunki Kim, Carly Fein, Laura H. Tang, Ting Wu, Matthew J. Marton, Senaka Peter, David P. Kelsen, Geoffr
Cancer Medicine.2021; 10(23): 8365. CrossRef
A novel form of immunotherapy using antigen peptides conjugated on PD-L1 antibody
Eun Ji Lee, Gun-Young Jang, Sung Eun Lee, Ji won Lee, Hee Dong Han, Yeong-Min Park, Tae Heung Kang
Immunology Letters.2021; 240: 137. CrossRef
Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival
Lei Tu, Renguo Guan, Hanting Yang, Yu Zhou, Weifeng Hong, Liheng Ma, Guangzhe Zhao, Min Yu
International Journal of Cancer.2020; 147(2): 423. CrossRef
Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis
Jiahang Mo, Xiao Hu, Lihu Gu, Bangsheng Chen, Parikshit Asutosh Khadaroo, Zefeng Shen, Lei Dong, Yuqi Lv, Marylin Nyaradzo Chitumba, Jiequan Liu
World Journal of Surgical Oncology.2020;[Epub] CrossRef
Prognostic value of PD-L1 expression on tumor cells combined with CD8+ TIL density in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy
Kathrin Gennen, Lukas Käsmann, Julian Taugner, Chukwuka Eze, Monika Karin, Olarn Roengvoraphoj, Jens Neumann, Amanda Tufman, Michael Orth, Simone Reu, Claus Belka, Farkhad Manapov
Radiation Oncology.2020;[Epub] CrossRef
PD-L1 induction in tumor tissue after hypofractionated thoracic radiotherapy for non-small cell lung cancer
Jaanika Narits, Hannes Tamm, Jana Jaal
Clinical and Translational Radiation Oncology.2020; 22: 83. CrossRef
Variation of PD-L1 expression in locally advanced cervical cancer following neoadjuvant chemotherapy
Yun Liang, Minghua Yu, Caiyun Zhou, Xiaojun Zhu
Diagnostic Pathology.2020;[Epub] CrossRef
Application of immune checkpoint inhibitors in EGFR-mutant non-small-cell lung cancer: from bed to bench
Rui Jin, Jing Zhao, Lexin Xia, Qin Li, Wen Li, Ling Peng, Yang Xia
Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
Independent Prognostic Value of Intratumoral Heterogeneity and Immune Response Features by Automated Digital Immunohistochemistry Analysis in Early Hormone Receptor-Positive Breast Carcinoma
Dovile Zilenaite, Allan Rasmusson, Renaldas Augulis, Justinas Besusparis, Aida Laurinaviciene, Benoit Plancoulaine, Valerijus Ostapenko, Arvydas Laurinavicius
Frontiers in Oncology.2020;[Epub] CrossRef
Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Lorenzo Galluzzi, Juliette Humeau, Aitziber Buqué, Laurence Zitvogel, Guido Kroemer
Nature Reviews Clinical Oncology.2020; 17(12): 725. CrossRef
Re-biopsy after first line treatment in advanced NSCLC can reveal changes in PD-L1 expression
Malene Støchkel Frank, Uffe Bødtger, Asbjørn Høegholm, Inger Merete Stamp, Julie Gehl
Lung Cancer.2020; 149: 23. CrossRef
The Mechanisms of PD-L1 Regulation in Non-Small-Cell Lung Cancer (NSCLC): Which Are the Involved Players?
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Cancers.2020; 12(11): 3129. CrossRef
The Dichotomous Role of Bone Marrow Derived Cells in the Chemotherapy-Treated Tumor Microenvironment
Avital Vorontsova, Tal Kan, Ziv Raviv, Yuval Shaked
Journal of Clinical Medicine.2020; 9(12): 3912. CrossRef
Adjuvant Chemotherapy Increases Programmed Death-Ligand 1 (PD-L1) Expression in Non–small Cell Lung Cancer Recurrence
Max Lacour, Stefanie Hiltbrunner, Seok-Yun Lee, Alex Soltermann, Elisabeth Jane Rushing, Davide Soldini, Walter Weder, Alessandra Curioni-Fontecedro
Clinical Lung Cancer.2019; 20(5): 391. CrossRef
PD-L1 Testing in Non-small Cell Lung Cancer: Past, Present, and Future
Hyojin Kim, Jin-Haeng Chung
Journal of Pathology and Translational Medicine.2019; 53(4): 199. CrossRef

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