Cancer Research and Treatment

Original Articles

Genomic Profiling Identified a Mutational Signature Related to Female in Non-Smoking Lung Adenocarcinoma: Jinman Zhuang, Yongsheng Yang, Xuezhen Chen, Guanying Zheng, Xiaopei Shen, Fei He, Baosong Xie; Received May 7, 2025 Accepted September 10, 2025 Published online September 11, 2025; DOI: https://doi.org/10.4143/crt.2025.489 [Accepted]

Abstract PDF: Purpose
Our aim was to illustrate mutational characteristic in non-smoking lung adenocarcinoma (LUAD) and to explore its relationship with clinical factors.
Materials and Methods
We included 86 non-smokers with LUAD and downloaded the clinical information, whole exon sequencing (WES), and RNA sequencing (RNA-seq) data from cBioPortal and TCGA website. NMF algorithm, “SomaticSignatures”, and “DeconstructSigs” were used to re-construct and infer new mutational signature. The similarity between COSMIC and re-constructed mutational signature was measured by cosine similarity. The enrichment status of signaling pathways was derived by GSEA. “pRRophetic” package was used to predict the sensitivity of adjuvant drug for cancer treatments.
Results
The most frequent driver genes in non-smoking LUAD were EGFR (59% in cBioPortal cohort, 68% in Fujian non-smoking LUAD cohort). We identified three new mutation signatures of LUAD in non-smokers and identified S2 as the most enriched signature in these non-smokers with LUAD. In cBioPortal and Fujian non-smoking LUAD cohort, the proportion of S2 was higher in females (p<0.05) and patients with TMB (p<0.01). Similar results were observed in non-smoking TCGA-LUAD cohort (P_female=0.0013, P_TMB<0.001). OXIDATIVE_PHOSPHORYLATION signaling pathway were most enriched in S2-enriched group (NES= 1.63). S2-enriched group had higher mutation rate of EGFR (p=0.003) and more drug sensitivity to metformin (p=0.035).
Conclusion
We identified a new mutational signature (S2) which is most enriched in LUAD in non-smokers and related to female and low-TMB. S2 mutational signature may help revealed female-related mutagenesis mechanisms and develop strategies for therapeutic of never-smoker lung adenocarcinoma.

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Genomic Insights into Innate Resistance in Early-Stage EGFR-Mutant Non-Small Cell Lung Cancer: A Comprehensive Analysis of Next-Generation Sequencing Data: Hayoung Seong, Soo Han Kim, Mi-Hyun Kim, Ahrong Kim, Ju Sun Song, Jung Seop Eom; Received January 28, 2025 Accepted August 19, 2025 Published online August 25, 2025; DOI: https://doi.org/10.4143/crt.2025.114 [Accepted]

Abstract PDF: Purpose
Comprehensive genomic profiling of early-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations remains limited. This study aimed to investigate genomic profiles of early- and advanced-stage EGFR-mutant NSCLC and identify potential innate resistance mechanisms to EGFR-tyrosine kinase inhibitors (TKIs) using targeted next-generation sequencing (NGS).
Materials and Methods
This retrospective observational study analyzed genomic profiles of patients with early-stage (IA–IIIA) and advanced-stage (IIIB–IV) EGFR-mutant NSCLC from the Lung Cancer NGS registry. Targeted NGS was performed to assess concurrent genetic alterations (GAs), tumor mutational burden (TMB), and variant allele frequency (VAF) of EGFR mutations.
Results
Overall, 160 patients (100 early-stage and 60 advanced-stage) were analyzed. The proportion of patients with concurrent GAs was not significantly different between stages (82.0% vs. 91.7%, p=0.092). Median TMB was 3.8 mutations/Mb in both stages, with no significant difference (p=0.206). However, the median VAF of EGFR mutations was significantly lower in early-stage compared to that in advanced-stage (19.3% vs. 29.6%, p=0.002). While TMB remained unchanged with disease progression (P = 0.192), VAF of EGFR mutations increased significantly (p<0.001). Moreover, the frequencies of concurrent single nucleotide variants and copy number variants were significantly lower in early-stage NSCLC.
Conclusion
Genomic heterogeneity in EGFR-mutant NSCLC arises early in tumorigenesis. The comparable TMB and lower VAF of EGFR mutations in early-stage disease suggest that innate resistance to EGFR-TKIs may be driven by concurrent GAs, supporting the consideration of combination therapies even in early-stage EGFR-mutant NSCLC.

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BTG1 Mutation Correlates with Inferior Prognosis in Diffuse Large B-Cell Lymphoma: Chun-Yu Shang, Wei Hua, Tong-Yao Xing, Kai-Xin Du, Yi-fan Wu, Yue Li, Hua Yin, Hao-Rui Shen, Li Wang, Jian-Yong Li, Rui Gao, Wei Xu, Jin-Hua Liang; Received May 8, 2025 Accepted July 30, 2025 Published online July 30, 2025; DOI: https://doi.org/10.4143/crt.2025.494 [Accepted]

Abstract PDF: Purpose
B celltranslocation gene 1 (BTG1) is a highly conserved gene and recurrently mutated in the MCD subtype of diffuse large B-cell lymphoma (DLBCL). The speciﬁc enrichment of BTG1 mutation (BTG1^mut) raises a potential hypothesis that they may actively contribute to DLBCL. However, the biological characteristics and prognostic significance of BTG1 in DLBCL remain to be explored. Therefore, the objective of our study was to evaluate the value of BTG1 in DLBCL.
Materials and Methods
The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Tumor tissue samples of DLBCL patients diagnosed in Jiangsu Province Hospital (JSPH) from 2021 to 2023 were collected for NGS, 195 samples were analyzed the gene expression levels using RNA-seq, among them, 40 samples were analyzed by untargeted metabolomic.
Results
We enrolled 2,379 DLBCL patients from 5 published studies and 243 DLBCL patients from Jiangsu Province Hospital (JSPH) cohort. 11.0% (262/2379) of patients were BTG1^mut in external cohort, compared with 25.1% (61/243) in the JSPH cohort. BTG1^mut was associated with adverse clinical features and was prone to involve testis. Patients with BTG1^mut exhibit inferior overall survival (OS). Furthermore, pathway enrichment analysis of the untargeted metabolomic showed that several meaningful pathways have been found such as amino acid metabolism and lipid metabolism.
Conclusion
BTG1 mutation was promising prognostic predictor for DLBCL. The mechanism driving different survival outcomes may be attributed to the tumor metabolic reprogramming.

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A Novel CD58 Mutation-Related Signature Predicts Prognosis Risk in Diffuse Large B-Cell Lymphoma Patients: Hui-Li Wang, Chun-Yu Shang, Wei Hua, Hua Yin, Yue Li, Jun-Heng Liang, Rui Gao, Bi-Hui Pan, Xin-Yu Zhang, Jia-Zhu Wu, Hao-Rui Shen, Li Wang, Jian-Yong Li, Jin-Hua Liang, Wei Xu; Received November 27, 2024 Accepted July 21, 2025 Published online July 28, 2025; DOI: https://doi.org/10.4143/crt.2024.1143 [Accepted]

Abstract PDF

Purpose
CD58, a ligand of the CD2 receptor on T cells and NK cells, is abnormally expressed in diffuse large B-cell lymphoma (DLBCL). However, data on the value of CD58 mutation (CD58mut) in DLBCL are limited. Here, we aimed to evaluate the characteristics and prognostic value of CD58^mut in DLBCL patients
Materials and Methods
The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Ultimately, 3025 DLBCL patients in published cohorts were enrolled in the final analysis. Among the 202 DLBCL patients in the Jiangsu Province Hospital (JSPH) cohort, all tumor tissue samples were collected to perform NGS and gene expression were analyzed via RNA-seq.
Results
We found that 8.2% (250/3025) of patients were CD58^mut in integrated cohort, whereas 11.3% (23/202) in JSPH cohort. CD58^mut patients exhibit inferior progression-free survival (PFS) (the integrated cohort: HR=0.96,95% CI:0.77–1.20, p=0.663 the JSPH cohort: HR=1.85,95% CI:0.85–4.04, p=0.052) and overall survival (OS) (the integrated cohort: HR=1.43,95% CI:1.15-1.77, p<0.001; the JSPH cohort: HR=2.40,95% CI:0.83–6.93, p=0.026). A model based on six signature genes (MRO, OXTR, RASL11A, RLN1, SIGLEC1 and PROM2) was constructed via machine learning. To optimize risk stratification and survival prediction for CD58^mut patients, biological mechanism of the poorer prognosis in high-risk group may be related to the greater abundance of immunosuppressive cells, especially M2 macrophages.
Conclusion
Our results indicated that CD58^mut could serve as a novel prognostic factor for DLBCL patients, and further exploration of personalized treatment strategies for high-risk DLBCL patients based on the risk score model is needed.

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ESAE-SDA: ensemble sparse autoencoder framework for epigenomics-informed snoRNA-disease associations prediction
Xinqing Jiang, Xiaojun Chen, Lifeng Xu, Feng Zhang, Jiawei Chen, Wenqian Zhang
BMC Bioinformatics.2025;[Epub] CrossRef

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General

Epidermal Growth Factor Receptor Aberrations Identified by Next-Generation Sequencing in Patients with Metastatic Cancers: Minkyue Shin, Dae-Ho Choi, Jaeyun Jung, Deok Geun Kim, Minae An, Sung Hee Lim, Seung Tae Kim, Jung Yong Hong, Se Hoon Park, Joon Oh Park, Kyoung-Mee Kim, Jeeyun Lee; Cancer Res Treat. 2025;57(4):932-941. Published online February 21, 2025; DOI: https://doi.org/10.4143/crt.2024.564

Abstract PDF Supplementary Material PubReader ePub: Purpose
The epidermal growth factor receptor (EGFR) is a therapeutic target with confirmed clinical efficacy for several cancer types. We aimed to identify EGFR aberrations and their associations with other genomic alterations in patients with metastatic diseases of various cancers.
Materials and Methods
We used real-world data from the next-generation sequencing (NGS) of 3,286 patients with metastatic cancer at the Samsung Medical Center. We analyzed the distribution of EGFR amplification, mutation, and fusion, as well as their correlations with microsatellite instability (MSI), tumor mutation burden (TMB), and other gene aberrations.
Results
A total of 3,286 patients were tested using NGS of a panel covering 523 cancer-related genes (TSO500, Illumina) as part of clinical practice between October 2019 and October 2022. Patients with lung cancer and gliomas were not included in the analysis. Of the 3,286 patients, 175 (5.3%) had EGFR amplification, 38 (1.2%) had EGFR mutations, and eight (0.2%) had EGFR fusion. All 175 patients with EGFR amplifications had microsatellite-stable tumors, but 102 had co-amplifications in other cancer-related genes, and 78 had mutations with clinical significance (tier I/II). Among the 38 patients with EGFR mutations, three (8%) showed MSI-high status, and 11 (29%) demonstrated high TMB (≥ 10 mutations/Mb). Among eight patients with EGFR fusion, three exhibited possible functionalities of the EGFR gene.
Conclusion
EGFR aberrations, mainly amplification, followed by mutation and fusion, were present in 6.4% of patients with metastatic solid tumors.

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Target-Enhanced Whole-Genome Sequencing Shows Clinical Validity Equivalent to Commercially Available Targeted Oncology Panel: Sangmoon Lee, Jin Roh, Jun Sung Park, Islam Oguz Tuncay, Wonchul Lee, Jung-Ah Kim, Brian Baek-Lok Oh, Jong-Yeon Shin, Jeong Seok Lee, Young Seok Ju, Ryul Kim, Seongyeol Park, Jaemo Koo, Hansol Park, Joonoh Lim, Erin Connolly-Strong, Tae-Hwan Kim, Yong Won Choi, Mi Sun Ahn, Hyun Woo Lee, Seokhwi Kim, Jang-Hee Kim, Minsuk Kwon; Cancer Res Treat. 2025;57(2):350-361. Published online September 19, 2024; DOI: https://doi.org/10.4143/crt.2024.114

Abstract PDF Supplementary Material PubReader ePub

Purpose
Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS.
Materials and Methods
This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches.
Results
TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making.
Conclusion
TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

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Whole-genome landscapes of 1,364 breast cancers
Ryul Kim, Jonghan Yu, Joonoh Lim, Brian Baek-Lok Oh, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Byung Joo Chae, Ji-Yeon Kim, Ga Eun Park, Bong Joo Kang, Pill Sun Paik, Soo Yeon Bae, Chang Ik Yoon, Young Joo Lee, Dooreh Kim, Kabsoo Shin, Ji Eun Lee, Jun Ka
Nature.2025;[Epub] CrossRef

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Breast cancer

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Cancer Res Treat. 2025;57(2):443-456. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296

Abstract PDF Supplementary Material PubReader ePub

Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Genomic and transcriptomic analyses of residual invasive triple-negative breast cancer after neoadjuvant chemotherapy in the prospective MIRINAE trial (a randomized phase II trial of adjuvant atezolizumab plus capecitabine compared to capecitabine; KCSG-B
S.-A. Im, K. Park, J. Koh, C. Park, K.H. Jung, J. Lee, H.K. Ahn, A. Lee, S.H. Sim, M.H. Kim, J.H. Kim, J.H. Kim, K.E. Lee, K.H. Park, J. Bae, M.H. Lee, S. Lim, H.J. Kim, D.-W. Lee, J.H. Jeong, K.S. Lee, J. Sohn, K.J. Suh, J.-Y. Kim, Y.J. Cha, J. Moon, C.-
ESMO Open.2025; 10(10): 105804. CrossRef

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Lung and Thoracic cancer

Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study: Songji Choi, Se Hyun Kim, Sejoon Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jin Won Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee; Cancer Res Treat. 2025;57(1):70-82. Published online August 7, 2024; DOI: https://doi.org/10.4143/crt.2024.046

Abstract PDF Supplementary Material PubReader ePub

Purpose
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

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Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics
Clelia Madeddu, Eleonora Lai, Manuela Neri, Elisabetta Sanna, Giulia Gramignano, Sonia Nemolato, Mario Scartozzi, Sabrina Giglio, Antonio Macciò
International Journal of Molecular Sciences.2025; 26(5): 2232. CrossRef
Prognostic and predictive implications of tumor suppressor gene alterations in non-small cell lung cancer
Marco Sposito, Lorenzo Belluomini, Riccardo Nocini, Jessica Insolda, Ilaria Mariangela Scaglione, Jessica Menis, Michele Simbolo, Antonio Lugini, Federica Buzzacchino, Francesco Verderame, Francesca Spinnato, Giuseppe Aprile, Lorenzo Calvetti, Mario Occhi
Scientific Reports.2025;[Epub] CrossRef
Enhanced tumor heterogeneity mediates poor prognosis in females with TP53 mutation in lung adenocarcinoma
Liudan Mai, Xinxin Yang, Chen Shao, Hongwei Yu, Fenqi Du, Jialu Liu, Yue Guan, Hao Li, Maopeng Yang, Hongxue Meng, Qiuju Zhang
International Journal of Biological Macromolecules.2025; 334: 149083. CrossRef

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Review Article

Recent Advances in Genomic Approaches for the Detection of Homologous Recombination Deficiency: Yoo-Na Kim, Doga C. Gulhan, Hu Jin, Dominik Glodzik, Peter J. Park; Cancer Res Treat. 2024;56(4):975-990. Published online July 17, 2024; DOI: https://doi.org/10.4143/crt.2024.154

Abstract PDF PubReader ePub

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

Citations

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Recommendations for Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer
Susan J. Hsiao, Destin Black, Kelly A. Devereaux, Ian S. Hagemann, Lawrence J. Jennings, Diana Mandelker, Vera A. Paulson, Michelle Shiller, Tracy L. Stockley, Eric Vail, Praveen Vikas, Anna Yemelyanova
The Journal of Molecular Diagnostics.2025; 27(8): 685. CrossRef
Homologous Recombination Deficiency in Ovarian and Breast Cancers: Biomarkers, Diagnosis, and Treatment
Bhaumik Shah, Muhammad Hussain, Anjali Seth
Current Issues in Molecular Biology.2025; 47(8): 638. CrossRef
Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends
Mi-Ran Ki, Dong Hyun Kim, Mohamed A. A. Abdelhamid, Seung Pil Pack
Biosensors.2025; 15(11): 737. CrossRef

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Original Articles

Gastrointestinal cancer

Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer: Seung-Young Oh, Giyong Jang, Jaeryuk Kim, Kyoung-Yun Jeong, Hyun Myong Kim, Yoon Jin Kwak, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Sung-Yup Cho, Jong-Il Kim, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1126-1135. Published online April 11, 2024; DOI: https://doi.org/10.4143/crt.2024.328

Abstract PDF PubReader ePub

Purpose
Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression.
Materials and Methods
Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation, and enrichment analysis were performed.
Results
As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in-silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the Rhoa^R129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked Rhoa^R129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families.
Conclusion
The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

Citations

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Hereditary diffuse gastric cancer: the evolution of a cancer syndrome
Lyvianne Decourtye-Espiard, Tanis Godwin, Parry Guilford
Journal of the Royal Society of New Zealand.2025; 55(6): 2636. CrossRef
A Comprehensive Review of Genetic Mutations Occurring in the Development and Progression of Gastric Cancer
Yalan Li, Qianqian Xu, Zhuo Chen, Mengting Chen, Kunyu Han, Zhuqing Zhang, Aling Shen, Xiaoyan Fu
Digestive Diseases.2025; 43(6): 630. CrossRef
Helicobacter pylori infection status and evolution of gastric cancer
Wenlin Zhang, Yuxin Zhang, Jing Ning, Weiwei Fu, Shigang Ding
Chinese Medical Journal.2025; 138(23): 3083. CrossRef
Current advances and challenges in Managing Hereditary Diffuse Gastric Cancer (HDGC): a narrative review
L. van der Sluis, J.M. van Dieren, R.S. van der Post, T.M. Bisseling
Hereditary Cancer in Clinical Practice.2024;[Epub] CrossRef

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Hematologic malignancy

Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma: Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2024;56(3):920-935. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.869

Abstract PDF Supplementary Material PubReader ePub

Purpose
The feasibility of sequencing circulating tumor DNA (ctDNA) in plasma as a biomarker to predict early relapse or poor prognosis in patients with follicular lymphoma (FL) receiving systemic immunochemotherapy is not clear.
Materials and Methods
We sequenced DNA from cell-free plasma that was serially obtained from newly diagnosed FL patients undergoing systemic immunochemotherapy. The mutation profiles of ctDNA at the time of diagnosis and at response evaluation and relapse and/or progression were compared with clinical course and treatment outcomes.
Results
Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed. Baseline sequencing detected mutations in all cases, with the major detected mutations being KMT2C (50%), CREBBP (45%), and KMT2D (45%). The concentration of ctDNA and tumor mutation burden showed a significant association with survival outcome. In particular, the presence of mutations in CREBBP and TP53 showed poor prognosis compared with patients without them. Longitudinal analysis of ctDNA using serially collected plasma samples showed an association between persistence or reappearance of ctDNA mutations and disease relapse or progression.
Conclusion
Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.

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Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Molecular pathology of lymphoma and its treatment strategies: from mechanistic elucidation to precision medicine
Zhongyu Wang, Shuai Feng, Xiangmei Yao, Renbin Zhao, Yujin Li, Maofeng Zheng, Zengzheng Li, Yajie Wang
Frontiers in Immunology.2025;[Epub] CrossRef
Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment
Alexis Claudel, Anne-Ségolène Cottereau, Emmanuel Bachy, Emmanuel Itti, Pierre Feugier, Cedric Rossi, Francois Lemonnier, Vincent Camus, Nicolas Daguindau, Guillaume Cartron, Emmanuelle Nicolas-Virelizier, Diana-Laure Mboumba, Christophe Cardoso, Côme Bom
Blood.2025; 146(8): 913. CrossRef
Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL
Chengqian Chen, Wei Guo, Haotian Wang, Luming Cao, Ou Bai
Frontiers in Immunology.2025;[Epub] CrossRef
Genetic analysis of cell-free DNA in follicular lymphoma in comparison with tissue-derived DNA
Yoshikazu Hori, Hiroki Hosoi, Mitsuo Osuga, Ryuta Iwamoto, Fumiyo Maekawa, Tadashi Okamura, Shogo Murata, Toshiki Mushino, Motomi Osato, Hitoshi Ohno, Nobuyuki Yamamoto, Shin-Ichi Murata, Yasuhiro Koh, Sonoki Takashi
Leukemia & Lymphoma.2025; : 1. CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review
Marie Hairing Enemark, Jonas Klejs Hemmingsen, Maja Lund Jensen, Robert Kridel, Maja Ludvigsen
International Journal of Molecular Sciences.2024; 25(20): 11179. CrossRef

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Lung and Thoracic cancer

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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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

8,527 View
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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.

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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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Breast cancer

Short-term Impact of Hormone Replacement Therapy on Risk of Breast Cancer in BRCA Mutation Carriers: A Nationwide Study in South Korea: Hye Yeon Kim, Jisoo Park, Seok Joo Moon, Sohyeon Jeong, Jin Hwa Hong, Jae Kwan Lee, Geum Joon Cho, Hyun-Woong Cho; Cancer Res Treat. 2024;56(1):143-148. Published online August 16, 2023; DOI: https://doi.org/10.4143/crt.2023.653

Abstract PDF PubReader ePub

Purpose
BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO.
Materials and Methods
A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups.
Results
There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278).
Conclusion
In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO.

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Epidemiology, Genetic Etiology, and Intervention of Premature Ovarian Insufficiency
Ting Guo, Hongyuan Liu, Bingying Xu, Yu Qi, Keyan Xu, Xinyi Wu, Xinmiao He, Yingying Qin, Zi-Jiang Chen
Endocrine Reviews.2025; 46(5): 621. CrossRef
Cancer du sein chez la femme en âge de procréer : problématiques autour du rôle des hormones
Ondine Dufour, Andréa Villeneuve, Blandine Courbiere, Alexandre de Nonneville
Bulletin du Cancer.2025; 112(7-8): 867. CrossRef
A contemporary review of breast cancer risk factors and the role of artificial intelligence
Orietta Nicolis, Denisse De Los Angeles, Carla Taramasco
Frontiers in Oncology.2024;[Epub] CrossRef

5,051 View
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Rare cancer

Clinical Features of Li-Fraumeni Syndrome in Korea: Ran Song, Sun-Young Kong, Wonyoung Choi, Eun-Gyeong Lee, Jaeyeon Woo, Jai Hong Han, Seeyoun Lee, Han-Sung Kang, So-Youn Jung; Cancer Res Treat. 2024;56(1):334-341. Published online August 9, 2023; DOI: https://doi.org/10.4143/crt.2023.794

Abstract PDF Supplementary Material PubReader ePub

Purpose
Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS.
Materials and Methods
Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected.
Results
Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively.
Conclusion
This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

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Association of DNA damage response pathway genes with rheumatoid arthritis risks: a case-control study
Muhammad Zahid Hussain, Muhammad Haris Khan, Muhammad Shahbaz Haris, Rida Huzaira, Ammarah Munawar, Maria Fazal Ul Haq, Rabia Shafique, Ishrat Mahjabeen
Scientific Reports.2025;[Epub] CrossRef
Consensus Statement: Recommendations on Actionable Biomarker Testing for Thyroid Cancer Management
Ozgur Mete, Andrée Boucher, Kasmintan A. Schrader, Omar Abdel-Rahman, Houda Bahig, Cheryl Ho, Olfat Kamel Hasan, Bernard Lemieux, Eric Winquist, Ralph Wong, Jonn Wu, Nicole Chau, Shereen Ezzat
Endocrine Pathology.2024; 35(4): 293. CrossRef

5,833 View
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2 Crossref

Lung and Thoracic cancer

Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma: Jae Seok Lee, Eun Kyung Kim, Kyung A Kim, Hyo Sup Shim; Cancer Res Treat. 2024;56(1):104-114. Published online July 24, 2023; DOI: https://doi.org/10.4143/crt.2023.728

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection.
Materials and Methods
Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI).
Results
In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025).
Conclusion
Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.

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Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA
Yoshihiko Taniguchi, Akihiro Tamiya, Mitsuo Osuga, Shun-ichi Isa, Keiichi Nakamura, Yasuyuki Mizumori, Tsutomu Shinohara, Hidetoshi Yanai, Katsumi Nakatomi, Masahide Oki, Masahide Mori, Tomohito Kuwako, Koji Yamazaki, Masahiro Shimada, Masahiko Ando, Yasu
Investigational New Drugs.2025;[Epub] CrossRef
A Novel CLTC::RPS6KB1 Fusion in a Poorly Differentiated Carcinoma Involving the Lung and Mediastinum
Mitchell Zhao, Nicholas Protopsaltis, Mina Sabet, Shulei Sun, Grace Lin, Farnaz Hasteh, Wei Song
International Journal of Surgical Pathology.2025; 33(6): 1526. CrossRef

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Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset: Ki Hyeong Lee, Byoung Chul Cho, Myung-Ju Ahn, Yun-Gyoo Lee, Youngjoo Lee, Jong-Seok Lee, Joo-Hang Kim, Young Joo Min, Gyeong-Won Lee, Sung Sook Lee, Kyung-Hee Lee, Yoon Ho Ko, Byoung Yong Shim, Sang-We Kim, Sang Won Shin, Jin-Hyuk Choi, Dong-Wan Kim, Eun Kyung Cho, Keon Uk Park, Jin-Soo Kim, Sang Hoon Chun, Jangyoung Wang, SeokYoung Choi, Jin Hyoung Kang; Cancer Res Treat. 2024;56(1):48-60. Published online June 27, 2023; DOI: https://doi.org/10.4143/crt.2023.453

Abstract PDF Supplementary Material PubReader ePub

Purpose
This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods
Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results
In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion
Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Citations

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Solid phase extraction and high-performance liquid chromatographic determination of lazertinib in human plasma
Yoshito Gando, Takeo Yasu
Drug Discoveries & Therapeutics.2025;[Epub] CrossRef
First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis
Jietao Ma, Xiaoxue Pang, Shuling Zhang, Letian Huang, Li Sun, Chengbo Han
Scientific Reports.2024;[Epub] CrossRef

9,236 View
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Clinical Validation of the Unparalleled Sensitivity of the Novel Allele-Discriminating Priming System Technology–Based EGFR Mutation Assay in Patients with Operable Non–Small Cell Lung Cancer: Il-Hyun Park, Dae-Soon Son, Yoon-La Choi, Ji-Hyeon Choi, Ji-Eun Park, Yeong Jeong Jeon, Minseob Cho, Hong Kwan Kim, Yong Soo Choi, Young Mog Shim, Jung Hee Kang, Suzy Park, Jinseon Lee, Sung-Hyun Kim, Byung-Chul Lee, Jhingook Kim; Cancer Res Treat. 2024;56(1):81-91. Published online June 20, 2023; DOI: https://doi.org/10.4143/crt.2023.408

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens.
Materials and Methods
In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee.
Results
The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients.
Conclusion
The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.

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Highly Sensitive 3D‐Nanoplasmonic‐Based Epidermal Growth Factor Receptor Mutation Multiplex Assay Chip for Liquid Biopsy
Ji Young Lee, Byeong‐Ho Jeong, Ho Sang Jung, Taejoon Kang, Yeonkyung Park, Jin Kyung Rho, Sung‐Gyu Park, Min‐Young Lee
Small Science.2024;[Epub] CrossRef
The Advantage of Targeted Next-Generation Sequencing over qPCR in Testing for Druggable EGFR Variants in Non-Small-Cell Lung Cancer
Adam Szpechcinski, Joanna Moes-Sosnowska, Paulina Skronska, Urszula Lechowicz, Magdalena Pelc, Malgorzata Szolkowska, Piotr Rudzinski, Emil Wojda, Krystyna Maszkowska-Kopij, Renata Langfort, Tadeusz Orlowski, Pawel Sliwinski, Mateusz Polaczek, Joanna Chor
International Journal of Molecular Sciences.2024; 25(14): 7908. CrossRef

5,939 View
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Gastrointestinal cancer

Specific Mutations in APC, with Prognostic Implications in Metastatic Colorectal Cancer: Huan Peng, Jun Ying, Jia Zang, Hao Lu, Xiaokai Zhao, Pengmin Yang, Xintao Wang, Jieyi Li, Ziying Gong, Daoyun Zhang, Zhiguo Wang; Cancer Res Treat. 2023;55(4):1270-1280. Published online April 24, 2023; DOI: https://doi.org/10.4143/crt.2023.415

Abstract PDF Supplementary Material PubReader ePub

Purpose
Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC.
Materials and Methods
Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed.
Results
APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations.
Conclusion
APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.

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In Silico Validation of OncoOrigin: An Integrative AI Tool for Primary Cancer Site Prediction with Graphical User Interface to Facilitate Clinical Application
Petar Brlek, Luka Bulić, Nidhi Shah, Parth Shah, Dragan Primorac
International Journal of Molecular Sciences.2025; 26(6): 2568. CrossRef
Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation
Muhammad Tufail, Can-Hua Jiang, Ning Li
Molecular Cancer.2025;[Epub] CrossRef
Investigating the Potential of Natural Agents for Colorectal Cancer Treatment with Molecular Modeling
Eda Arabacı, Nil Sazlı, Deniz Karataş
Karadeniz Fen Bilimleri Dergisi.2025; 15(2): 787. CrossRef
A set cover algorithm identifies minimal circulating tumour DNA sequencing targets for colorectal cancer detection
Kit Moloney-Geany, Michael A. Black, Robert C. Day, Parry Guilford, Michael J. Dunnet
Scientific Reports.2025;[Epub] CrossRef
Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies
Neelakanta Sarvashiva Kiran, Chandrashekar Yashaswini, Rahul Maheshwari, Sankha Bhattacharya, Bhupendra G. Prajapati
ACS Pharmacology & Translational Science.2024; 7(4): 967. CrossRef
Clinical implications of PD-L1 expression and pathway-related molecular subtypes in advanced Asian colorectal cancer patients
Qingqing Qiu
American Journal of Cancer Research.2024; 14(2): 796. CrossRef
Mechanism of APC truncation involved in colorectal cancer tumorigenesis (Review)
Tuya Wang, Jing Fu, Ye Huang, Chun Fu
Oncology Letters.2024;[Epub] CrossRef

9,561 View
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Lung and Thoracic cancer

Should We Perform Repeated Re-biopsy for the Detection of T790M Mutation?: Saerom Kim, Soo Han Kim, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Jung Seop Eom; Cancer Res Treat. 2023;55(4):1190-1197. Published online April 17, 2023; DOI: https://doi.org/10.4143/crt.2023.320

Abstract PDF PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) T790M mutations have been detected in the second or third rebiopsy, even if the T790M mutation was not identified in the first rebiopsy. This meta-analysis investigated the EGFR T790M mutation detection rates and its additional advantages with repeated rebiopsies.
Materials and Methods
We searched through the PubMed and EMBASE databases up to June 2022. Studies reporting rebiopsy to identify the EGFR T790M mutation in case of disease progression among patients with advanced non-small cell lung cancer and multiple rebiopsies were included. The quality of the included studies was checked using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.
Results
Eight studies meeting the eligibility criteria, reporting 1,031 EGFR mutation–positive patients were selected. The pooled EGFR T790M mutation detection rate of the first and repeated rebiopsies were 0.442 (95% confidence interval [CI], 0.411 to 0.473; I²=84%; p < 0.01) and 0.465 (95% CI, 0.400 to 0.530; I²=69%; p < 0.01), respectively. Overall, the pooled detection rate of EGFR T790M mutation was 0.545 (95% CI, 0.513 to 0.576), which increased by 10.3% with repeated rebiopsies.
Conclusion
This meta-analysis identified that repeated rebiopsy increases the detection rate of EGFR T790M mutation by 10.3%, even if EGFR T790M mutation is not detected in the first rebiopsy. Our results indicate that the spatiotemporal T790M heterogeneity can be overcome with repeated rebiopsy.

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Enhanced Detection of Druggable Mutations in Non–Small Cell Lung Cancer Using Targeted Collection of Bronchial Washing Fluid Compared With Plasma and Tumor Tissue
Mi-Hyun Kim, Soo Han Kim, Hayoung Seong, Jung Seop Eom
JCO Precision Oncology.2025;[Epub] CrossRef
A Multicenter Study on Unnecessary Rebiopsies in CT‐Guided Percutaneous Transthoracic Needle Biopsy of Pulmonary Lesions
Yangfan He, Huanhuan He, Yubo Cai, Shanshan Lyu, Zhengyi Zhou, Chengyou Zheng, Xinke Zhang, Jinling Duan, Jierong Chen, Jiewei Chen
Cancer Medicine.2025;[Epub] CrossRef
Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
Frontiers in Oncology.2024;[Epub] 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
Rebiopsie tumorale : quand ? pour qui ? pourquoi ? comment ?
V. Fallet
Revue des Maladies Respiratoires Actualités.2023; 15(2): 2S121. CrossRef

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Genomic Characteristics and the Potential Clinical Implications in Oligometastatic Non–Small Cell Lung Cancer: Rongxin Liao, Kehong Chen, Jinjin Li, Hengqiu He, Guangming Yi, Mingfeng Huang, Rongrong Chen, Lu Shen, Xiaoyue Zhang, Zaicheng Xu, Zhenzhou Yang, Yuan Peng; Cancer Res Treat. 2023;55(3):814-831. Published online January 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1315

Abstract PDF Supplementary Material PubReader ePub

Purpose
Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis.
Materials and Methods
We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity.
Results
We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation.
Conclusion
Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

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Frequency and Prognostic Impact of Local Ablation Therapy for Oligoprogression in Non‐Small Cell Lung Cancer
Daisuke Morinaga, Jun Sakakibara‐Konishi, Ryohei Kamada, Masahiro Kashima, Kosuke Tsuji, Shotaro Ito, Megumi Furuta, Tetsuaki Shoji, Yuta Takashima, Hidenori Kitai, Yasuyuki Ikezawa, Hiroshi Taguchi, Tatsuya Kato, Yoshiki Shinomiya, Kanako C Hatanaka, Yut
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Augusto Valdivia, Pau Mascaro-Baselga, Clara Salva-de Torres, Abraham Geng-Cahuayme, Sara Torresan, Jesus Yaringaño, Ilaria Priano, Patricia Iranzo, Nuria Pardo, Laura Masfarre, Oriol Mirallas, Karen Farfan, Susana Cedres, Pedro Rocha, Alex Martinez-Marti
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Mandy Jongbloed, Martina Bortolot, Leonard Wee, Jarno W.J. Huijs, Murillo Bellezo, Rianne D.W. Vaes, Frank Aboubakar Nana, Koen J. Hartemink, Dirk K.M. De Ruysscher, Lizza E.L. Hendriks
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Genomic characteristics of PD-L1-Induced resistance to EGFR-TKIs in lung adenocarcinoma
Guangming Yi, Fanghao Cai, Liangzhong Liu, Rongxin Liao, Xuan Jiang, Zhenzhou Yang, Xiaoyue Zhang
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General

Validation and Clinical Application of ONCOaccuPanel for Targeted Next-Generation Sequencing of Solid Tumors: Moonsik Kim, Changseon Lee, Juyeon Hong, Juhee Kim, Ji Yun Jeong, Nora Jee-Young Park, Ji-Eun Kim, Ji Young Park; Cancer Res Treat. 2023;55(2):429-441. Published online November 25, 2022; DOI: https://doi.org/10.4143/crt.2022.891

Abstract PDF Supplementary Material PubReader ePub

Purpose
Targeted next-generation sequencing (NGS) is widely used for simultaneously detecting clinically informative genetic alterations in a single assay. Its application in clinical settings requires the validation of NGS gene panels. In this study, we aimed to validate a targeted hybridization capture-based DNA panel (ONCOaccuPanel) using the Illumina MiSeq sequencing platform. The panel allows the simultaneous detection of single-nucleotide variants (SNVs), insertions, deletions, and copy number changes of 323 genes and fusions of 17 genes in solid tumors.
Materials and Methods
We used 16 formalin-fixed paraffin-embedded (FFPE) tumor samples with previously known genetic mutations and one reference material (HD827) for validation. Moreover, we sequenced an additional 117 FFPE tumor samples to demonstrate the clinical utility of this panel.
Results
Validation revealed a 100% positive percentage agreement and positive predictive value for the detection of SNVs, insertions, deletions, copy number changes, fusion genes, and microsatellite instability–high types. We observed high levels of reproducibility and repeatability (R2 correlation coefficients=0.96-0.98). In the limit of detection assessment, we identified all clinically relevant genes with allele frequencies > 3%. Furthermore, the clinical application of ONCOaccuPanel using 117 FFPE samples demonstrated robust detection of oncogenic alterations. Oncogenic alterations and targetable genetic alterations were detected in 98.2% and 27.4% cases, respectively.
Conclusion
ONCOaccuPanel demonstrated high analytical sensitivity, reproducibility, and repeatability and is feasible for the detection of clinically relevant mutations in clinical settings.

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Risk prediction criteria for the primary hepatic perivascular epithelioid cell tumour family, including angiomyolipoma: analysis of 132 cases with a literature review
Youngeun Yoo, Jihun Kim, In Hye Song
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Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma
In Hye Song, Bokyung Ahn, Young Soo Park, Deok Hoon Kim, Seung-Mo Hong
Cancer Research and Treatment.2025; 57(2): 492. CrossRef
Evaluation of potential of targeted sequencing through mutational signature simulation
Keisuke Kodama, Yiwei Ling, Hiroshi Ichikawa, Toshifumi Wakai, Shujiro Okuda, Divijendra Natha Reddy Sirigiri
PLOS One.2025; 20(6): e0326071. CrossRef
Generation of orthotopic intracranial glioblastoma patient-derived xenograft models: insights into extrachromosomal DNA-driven MYC(N) and PDGFRA oncogene amplification and preliminary therapeutic evaluation
Thi-Anh-Thuy Tran, Sinae An, Junghyun Lim, Young-Hee Kim, Ahyeon Shim, Taewoo Han, Hawsan Kim, Sue-Jee Park, Yeong Jin Kim, Kyung-Sub Moon, In-Young Kim, Shin Jung, Chul Won Lee, Kyung-Hwa Lee, Ae Kyung Park, Tae-Young Jung
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Primary Solid Pseudopapillary Tumor of the Ovary: A Case Report and Review of the Literature
Juhun Lee, Seung Ho Song, In Hee Lee, Dong Ja Kim, Hyun Jung Lee
Journal of Clinical Medicine.2024; 13(10): 2791. CrossRef
Genome-scale mutational signature analysis in archived fixed tissues
Bérénice Chavanel, François Virard, Vincent Cahais, Claire Renard, Cécilia Sirand, Kim M. Smits, Leo J. Schouten, Béatrice Fervers, Barbara Charbotel, Behnoush Abedi-Ardekani, Michael Korenjak, Jiri Zavadil
Mutation Research - Reviews in Mutation Research.2024; 794: 108512. CrossRef
Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer
Jinahn Jeong, Deokhoon Kim, Yeon-Mi Ryu, Ja-Min Park, Sun Young Yoon, Bokyung Ahn, Gi Hwan Kim, Se Un Jeong, Hyun-Jung Sung, Yong Il Lee, Sang-Yeob Kim, Yong Mee Cho
Journal of Pathology and Translational Medicine.2024; 58(5): 229. CrossRef
CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas
Sang Hyuk Lee, Tae Gyu Kim, Kyeong Hwa Ryu, Seok Hyun Kim, Young Zoon Kim
Biomedicines.2024; 12(10): 2256. CrossRef
Comparison of immunohistochemistry and next-generation sequencing results in oncogenic PTEN missense mutations
Moonsik Kim, Jinhee Kim, An Na Seo, Ji Yun Jeong, Nora Jee-Young Park, Gun Oh Chong, Dae Gy Hong, Ji Young Park
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BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy
Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim
Journal of Pathology and Translational Medicine.2023; 57(6): 323. CrossRef
Clinical Application of the Association between Genetic Alteration and Intraoperative Fluorescence Activity of 5-Aminolevulinic Acid during the Resection of Brain Metastasis of Lung Adenocarcinoma
Hyeon Yeong Jeong, Won Jun Suh, Seung Hwan Kim, Taek Min Nam, Ji Hwan Jang, Kyu Hong Kim, Seok Hyun Kim, Young Zoon Kim
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Lung and Thoracic cancer

Real World Characteristics and Clinical Outcomes of HER2-Mutant Non–Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing: Beung-Chul Ahn, Ye-Jeong Han, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim; Cancer Res Treat. 2023;55(2):488-497. Published online November 9, 2022; DOI: https://doi.org/10.4143/crt.2022.359

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents.
Materials and Methods
Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed.
Results
The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively.
Conclusion
Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.

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Targeted therapy for older patients with an oncogene driven non-small cell lung cancer: Recommendations from a SIOG expert group
L. Decoster, D.R. Camidge, J.A. Fletcher, A. Addeo, A. Greystoke, K. Kantilal, L.Bigay Game, R. Kanesvaran, F. Gomes
Lung Cancer.2025; 200: 108087. CrossRef
HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With HER2 Alterations: A Phase Ia Dose-Escalation Study
John V. Heymach, Frans Opdam, Minal Barve, Hai-Yan Tu, Yi-Long Wu, David Berz, Lukas Schröter, Yanick Botilde, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto
Journal of Clinical Oncology.2025; 43(11): 1337. CrossRef
Targeting HER2 in lung cancers: Evolving treatment landscape and drug development strategies
Daniel Reinhorn, Mor Moskovitz, William D. Tap, Bob T. Li
Cancer.2025;[Epub] CrossRef
Real-world therapeutic strategies and survival outcomes in advanced HER2-mutant non-small cell lung cancer
Ruei-Lin Sun, Pei-Ya Liao, Ying-Ting Liao, Yi-Chen Yeh, Chi-Lu Chiang, Yuh-Min Chen, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Hsu-Ching Huang, Chia-I Shen, Yen-Han Tseng, Yen-Hsiang Huang, Yung-Hung Luo, Tsung-Ying Yang
Journal of the Chinese Medical Association.2025; 88(4): 307. CrossRef
Genomic and clinical characterization of HER2 exon 20 mutations in non-small cell lung cancer: insights from a multicenter study in South China
Yating Hou, Xingyang Xue, Zhuoyun Zhang, Dahai Mai, Wei Luo, Mingyu Zhou, Zichuan Liu, Yisheng Huang
BMC Cancer.2025;[Epub] CrossRef
Survival and prognostic factors of HER2-mutant advanced non-small cell lung cancer with brain metastases
Qian Zhang, Yehao Yang, Mingying Xie, Zichao Zhou, Haicheng Wu, Wanchen Zhai, Yunfei Chen, Kaiyan Chen, Shichao Zhou, Hui Li, Yun Fan
Lung Cancer.2025; 205: 108616. CrossRef
HER2 in Non-Small Cell Lung Cancer (NSCLC): Evolution of the Therapeutic Landscape and Emerging Drugs—A Long Way to the Top
Pamela Trillo Aliaga, Gianluca Spitaleri, Ilaria Attili, Carla Corvaja, Elena Battaiotto, Panagiotis Agisilaos Angelopoulos, Ester Del Signore, Antonio Passaro, Filippo de Marinis
Molecules.2025; 30(12): 2645. CrossRef
Nonclinical and Clinical Assessments of an Optimized Tablet Formulation of the Novel HER2-Selective Tyrosine Kinase Inhibitor Zongertinib: Focus on Relative Bioavailability and Impact of Variation of Gastric pH
Stefan Wölke, Behbood Sadrolhefazi, Habib Esmaeili, Sven Wind, Simone M. Blattner, Guanfa Gan, Dongmei Qiang, Andrea Schirmer, Fabian Müller
Molecular Pharmaceutics.2025; 22(11): 6522. CrossRef
Relative Bioavailability of Zongertinib, an Orally Administered HER2-Selective Tyrosine Kinase Inhibitor, under Fed and Fasted Conditions in Healthy Male Participants: Results from Two Randomized, Open-Label, Crossover Studies
Hélène Pereira, Stefan Wölke, Behbood Sadrolhefazi, Habib Esmaeili, Sven Wind, Guanfa Gan, Fabian Müller, David Minich, Kerstin Bader, Rolf Grempler, Yeuk Ki Law, Philipp M. Roessner
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Real-World Characteristics, Treatment Patterns, and Outcomes in Advanced HER2 (ERBB2)-Mutant Non-Small Cell Lung Cancer: A Retrospective Study of Single Centers in France and Germany
Petros Christopoulos, Christin Assmann, Lirong Zhang, Kyle Dunton, Ahmed Ali, Mehmet Berktas, Lisa Delmastro, Alessandria Strübing, Yan Xiong, Sarah Lay-Flurrie, Pooja Hindocha, Tarana Mehdikhanova, Nicolas Girard
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Trastuzumab Deruxtecan for ERBB2-Mutant Metastatic Non–Small Cell Lung Cancer With or Without Brain Metastases
Pasi A. Jänne, David Planchard, Koichi Goto, Egbert F. Smit, Adrianus Johannes de Langen, Yasushi Goto, Kiichiro Ninomiya, Toshio Kubo, Maurice Pérol, Enriqueta Felip, Hidetoshi Hayashi, Kazuhiko Nakagawa, Junichi Shimizu, Misako Nagasaka, Kaline Pereira,
JAMA Network Open.2025; 8(11): e2543107. CrossRef
Prognostic factors in non-metastatic HER2 ‘low’ and HER2 ‘negative’ breast cancer: single institute experience
Alper Türkel, Mutlu Doğan, Elif Sertesen, Cengiz Karaçin, Sultan Çiğdem Irkkan, Öztürk Ateş
Wiener klinische Wochenschrift.2024; 136(11-12): 340. CrossRef
Clinicopathologic and Molecular Characteristics of HER2 (ERBB2)-Altered Non–Small Cell Lung Cancer: Implications for Precision Medicine
Yurimi Lee, Boram Lee, Yoon-La Choi, Dong-Wook Kang, Joungho Han
Modern Pathology.2024; 37(6): 100490. CrossRef
Current status and breakthroughs in treating advanced non-small cell lung cancer with EGFR exon 20 insertion mutations
Meng Hu, Congying Zhong, Jiabing Wang, JinQin Chen, Tao Zhou
Frontiers in Immunology.2024;[Epub] CrossRef
Efficacy of chemotherapy plus immune checkpoint inhibitors in patients with non-small cell lung cancer who have rare oncogenic driver mutations: a retrospective analysis
Teppei Yamaguchi, Junichi Shimizu, Reiko Matsuzawa, Naohiro Watanabe, Yoshitsugu Horio, Yutaka Fujiwara
BMC Cancer.2024;[Epub] CrossRef
Antibody–Drug Conjugates for the Treatment of Non-Small Cell Lung Cancer with Central Nervous System Metastases
David J. H. Bian, Sara F. Cohen, Anna-Maria Lazaratos, Nathaniel Bouganim, Matthew Dankner
Current Oncology.2024; 31(10): 6314. CrossRef
Real-World Clinical Outcomes for Patients with EGFR and HER2 Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer
Kelly Li, Ian Bosdet, Stephen Yip, Cheryl Ho, Janessa Laskin, Barbara Melosky, Ying Wang, Sophie Sun
Current Oncology.2023; 30(8): 7099. CrossRef

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EGFR Mutation–Positive Unresectable Stage III Non-Squamous Lung Cancer Is Associated with a High Incidence of Brain Metastasis: Hongsik Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn; Cancer Res Treat. 2023;55(2):498-505. Published online October 4, 2022; DOI: https://doi.org/10.4143/crt.2022.388

Abstract PDF PubReader ePub

Purpose
The impact of epidermal growth factor receptor (EGFR) mutation in locally advanced non–small cell lung cancer (NSCLC) remains controversial. This study was conducted to investigate the clinical outcomes and recurrence patterns after definitive chemoradiotherapy (CRT) in patients with unresectable stage III non-squamous-cell lung cancer according to EGFR mutation status.
Materials and Methods
We retrospectively reviewed 604 patients with pathologically confirmed stage III NSCLC who were treated with definitive CRT and were examined for EGFR mutation at Samsung Medical Center, Korea, from January 2013 to December 2018. Among them, we identified 236 patients with stage III non-squamous-cell lung cancer who were treated with definitive CRT and were examined for EGFR mutation status. We analyzed the frequency of EGFR mutation, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and recurrence pattern.
Results
Among 236 patients, EGFR mutation was detected in 71 patients (30.1%) and the median follow-up duration was 41.7 months. There were no significant differences in PFS (9.9 vs. 10.9 months, p=0.236), and ORR to CRT (93.0% vs. 90.3%, p=0.623) according to EGFR mutation status. However, the EGFR mutant group showed significantly higher recurrence (88.7% vs. 75.2%, p=0.022), distant metastasis (76.1% vs. 61.2%, p=0.036) rates, especially brain (38.0% vs. 12.7%, p < 0.001), and better median OS (59.2 vs. 41.3 months, p=0.037) compared with patients without EGFR mutation.
Conclusion
Patients with EGFR mutation–positive unresectable stage III non-squamous lung cancer exhibited higher recurrence and distant metastasis rates, especially brain metastasis.

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TFAP2A facilitates the metastasis and radioresistance of esophageal cancer by promoting EGFR transcription
Jinjin Yuan, Junqi Liu, Ruitai Fai, Zongwen Liu
Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(8): 10239. CrossRef
Cost-Effectiveness of Adjuvant Osimertinib With and Without Chemotherapy for Surgically Resected NSCLC
Angelos Vasilopoulos, Alexander Pohlman, Ayham Odeh, K. Robert Shen, Julia M. Coughlin, Zaid M. Abdelsattar
JTO Clinical and Research Reports.2025; 6(6): 100833. CrossRef
Unresectable stage III non-small-cell lung cancer: state of the art and challenges
Jordi Remon, Antonin Levy, Romane Gille, Isabelle Martel-Lafay, Martina Bortolot, Lizza E. L. Hendriks, Corinne Faivre-Finn, Natasha Leighl, Martin Reck, Maurice Pérol
Nature Reviews Clinical Oncology.2025;[Epub] CrossRef
Prognostic Factors in Postoperative Brain Metastases Derive From Non-small Cell Lung Cancer: A Retrospective Analysis
Haibin Chen, Liang Sun, Zhi Yang, Yuanyuan Qu, Nanyang Tong, Caixing Sun, Liang Xia
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Brain metastasis screening in the molecular age
Joanna K Tabor, Amanda Onoichenco, Vinayak Narayan, A Gabriella Wernicke, Randy S D’Amico, Morana Vojnic
Neuro-Oncology Advances.2023;[Epub] CrossRef

6,884 View
261 Download
9 Web of Science
5 Crossref

Breast cancer

Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation: Ju Won Kim, Hyo Eun Kang, Jimi Choi, Seung Gyu Yun, Seung Pil Jung, Soo Yeon Bae, Ji Young You, Yoon-Ji Choi, Yeul Hong Kim, Kyong Hwa Park; Cancer Res Treat. 2023;55(1):155-166. Published online June 8, 2022; DOI: https://doi.org/10.4143/crt.2021.1567

Abstract PDF Supplementary Material PubReader ePub

Purpose
BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants.
Materials and Methods
Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity.
Results
A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w.
Conclusion
We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

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Clinico-Pathological Factors Determining Recurrence of Phyllodes Tumors of the Breast: The 25-Year Experience at a Tertiary Cancer Centre
Baijaeek Sain, Arnab Gupta, Aruni Ghose, Sudip Halder, Vishal Mukherjee, Samir Bhattacharya, Radha Raman Mondal, Aditya Narayan Sen, Bijan Saha, Shravasti Roy, Stergios Boussios
Journal of Personalized Medicine.2023; 13(5): 866. CrossRef

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Lung and Thoracic cancer

The Feasibility of Using Biomarkers Derived from Circulating Tumor DNA Sequencing as Predictive Classifiers in Patients with Small-Cell Lung Cancer: Yu Feng, Yutao Liu, Mingming Yuan, Guilan Dong, Hongxia Zhang, Tongmei Zhang, Lianpeng Chang, Xuefeng Xia, Lifeng Li, Haohua Zhu, Puyuan Xing, Hongyu Wang, Yuankai Shi, Zhijie Wang, Xingsheng Hu; Cancer Res Treat. 2022;54(3):753-766. Published online October 5, 2021; DOI: https://doi.org/10.4143/crt.2021.905

Abstract PDF Supplementary Material PubReader ePub

Purpose
To investigate the feasibility of biomarkers based on dynamic circulating tumor DNA (ctDNA) to classify small cell lung cancer (SCLC) into different subtypes.
Materials and Methods
Tumor and longitudinal plasma ctDNA samples were analyzed by next-generation sequencing of 1,021 genes. PyClone was used to infer the molecular tumor burden index (mTBI). Pre-treatment tumor tissues [T1] and serial plasma samples were collected (pre-treatment [B1], after two [B2], six [B3] cycles of chemotherapy and at progression [B4]).
Results
Overall concordance between T1 and B1 sequencing (n=30) was 66.5%, and 89.5% in the gene of RB1. A classification method was designed according to the changes of RB1 mutation, named as subtype Ⅰ (both positive at B1 and B2), subtype Ⅱ (positive at B1 but negative at B2), and subtype Ⅲ (both negative at B1 and B2). The median progressive-free survival for subtype Ⅰ patients (4.5 months [95%CI: 2.6-5.8]) was inferior to subtype Ⅱ (not reached, p<0.0001) and subtype Ⅲ (10.8 months [95%CI: 6.0-14.4], p=0.002). The median overall survival for subtype Ⅰ patients (16.3 months [95%CI: 5.3-22.9]) was inferior to subtype Ⅱ (not reached, p=0.01) and subtype Ⅲ (not reached, p=0.02). Patients with a mTBI dropped to zero at B2 had longer median overall survival (not reached vs. 19.5 months, p=0.01). The changes of mTBI from B4 to B1 were sensitive to predict new metastases, with a sensitivity of 100% and a specificity of 85.7%.
Conclusion
Monitoring ctDNA based RB1 mutation and mTBI provided a feasible tool to predict the prognosis of SCLC.

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Roya Behrouzi, Alexandra Clipson, Kathryn L. Simpson, Fiona Blackhall, Dominic G. Rothwell, Caroline Dive, Florent Mouliere
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Sara Santamaria, Barbara Cardinali, Matteo Rovere, Silvia Marconi, Simone Nardin, Gianluca Sacco, Lucrezia Barcellini, Lucia Del Mastro, Carlo Genova, Simona Coco
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Natalia Galant, Anna Grenda, Paweł Krawczyk, Mateusz Pięt, Janusz Milanowski
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Helena Linardou, Kyriaki Papadopoulou, Nikolaos Korfiatis, Anna Goussia, Epaminondas Samantas, Gerasimos Aravantinos, Athina Christopoulou, Nikolaos Spathas, Elena Fountzilas, Amanda Psyrri, Georgia-Angeliki Koliou, Soultana Meditskou, Epaminondas Kosmas,
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Roya Behrouzi, Fiona Blackhall
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Changshu Li, Jun Shao, Peiyi Li, Jiaming Feng, Jingwei Li, Chengdi Wang
Cancer Letters.2023; 577: 216365. CrossRef
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Fan Yang, Min Tang, Liang Cui, Jing Bai, Jiangyong Yu, Jiayi Gao, Xin Nie, Xu Li, Xuefeng Xia, Xin Yi, Ping Zhang, Lin Li
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Ugo Testa, Elvira Pelosi, Germana Castelli
Onco.2022; 2(3): 186. 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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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
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General

Attitudes toward Risk-Reducing Mastectomy and Risk-Reducing Salpingo-oophorectomy among Young, Unmarried, Healthy Women in Korea: Boyoung Park, Dongwon Kim, Jiyoung Kim, Bom Yi Lee, Junghyun Yoon, Sung-Won Kim; Cancer Res Treat. 2022;54(2):375-382. Published online August 9, 2021; DOI: https://doi.org/10.4143/crt.2021.449

Abstract PDF PubReader ePub

Purpose
This study investigated the attitudes toward risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) as cancer prevention options for BRCA1/2 carriers in healthy, young, unmarried Korean women.
Materials and Methods
A nationally representative sample of 600 women, aged 20-39 years, completed a questionnaire on sociodemographic variables, preference for genetic testing, and intention to undergo risk-reducing surgeries after receiving information on the cancer risk of BRCA1/2 mutations and benefits of risk-reducing surgeries.
Results
A total of 54.7% and 57.7% had the intention to undergo RRM and RRSO, respectively, on the assumption that they were BRCA1/2 carriers. Older age and no intention to undergo genetic testing were associated with a reduced likelihood of undergoing RRM (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.14 to 0.61 for age 35-39 years and OR, 0.35; 95% CI, 0.20 to 0.62 for no intention for genetic testing) and RRSO (OR, 0.39; 95% CI, 0.19 to 0.79 for age 35-39 years and OR, 0.30; 95% CI, 0.17 to 0.53 for no intention for genetic testing). Women who chose to be single were likely to undergo risk-reducing surgeries (OR, 1.67; 95% CI, 1.07 to 2.60 for RRM and OR, 1.56; 95% CI, 1.00 to 2.44 for RRSO).
Conclusion
More than 50% of healthy, unmarried, young Korean women were inclined to undergo prophylactic surgeries if they were BRCA1/2 mutation carriers. Further studies on decision-making process for cancer prevention in individuals at high risk for cancer need to be conducted.

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A Scoping Review of Primary Breast Cancer Risk Reduction Strategies in East and Southeast Asia
Filipa Alpeza, Christine Kim Yan Loo, Qingyuan Zhuang, Mikael Hartman, Serene Si Ning Goh, Jingmei Li
Cancers.2025; 17(2): 168. CrossRef
Prevention and empowerment: cultural influences on prophylactic surgical decisions among BRCA mutation carriers in east Asia
Teng Qi, Hanqing Zhao
The Lancet Oncology.2025; 26(9): 1142. CrossRef
Impact of graphical display on the intention to undergo risk-reducing salpingo-oophorectomy and mastectomy in individuals positive for BRCA pathogenic variant
Yoon-Jung Choi, Younju Park, Boyoung Park, Heejung Chae, So-Youn Jung, Kum Hei Ryu, Myong Cheol Lim, Soo Jin Park, Yoon Jung Chang, Sun-Young Kong
Scientific Reports.2024;[Epub] CrossRef

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Lung and Thoracic cancer

Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Hyojin Kim, Hyun Jung Kwon, Eun Sun Kim, Soohyeon Kwon, Kyoung Jin Suh, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Jin-Haeng Chung; Cancer Res Treat. 2022;54(2):424-433. Published online July 7, 2021; DOI: https://doi.org/10.4143/crt.2021.583

Abstract PDF Supplementary Material PubReader ePub

Purpose
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non–small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.
Materials and Methods
This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.
Results
Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832).
Conclusion
The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

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Microdroplet-enhanced chip platform for high-throughput immunotherapy marker screening from extracellular vesicle RNAs and membrane proteins
Chuanhao Tang, Zaizai Dong, Shi Yan, Bing Liu, Zhiying Wang, Long Cheng, Feng Liu, Hong Sun, Yimeng Du, Lu Pan, Yuhao Zhou, Zhiyuan Jin, Libo Zhao, Nan Wu, Lingqian Chang, Xiaojie Xu
Biosensors and Bioelectronics.2025; 267: 116748. CrossRef
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Uraquitan Lima Filho, Tiago Alexandre Pais, Ricardo Jorge Pais
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Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial
Cheol-Kyu Park, Ha Ra Jun, Hyung-Joo Oh, Ji-Young Lee, Hyun-Ju Cho, Young-Chul Kim, Jeong Eun Lee, Seong Hoon Yoon, Chang Min Choi, Jae Cheol Lee, Sung Yong Lee, Shin Yup Lee, Sung-Min Chun, In-Jae Oh
Cells.2023; 12(9): 1246. CrossRef
Unveiling the role of regulatory T cells in the tumor microenvironment of pancreatic cancer through single-cell transcriptomics and in vitro experiments
Wei Xu, Wenjia Zhang, Dongxu Zhao, Qi Wang, Man Zhang, Qiang Li, Wenxin Zhu, Chunfang Xu
Frontiers in Immunology.2023;[Epub] CrossRef
Facilitating “Omics” for Phenotype Classification Using a User-Friendly AI-Driven Platform: Application in Cancer Prognostics
Uraquitan Lima Filho, Tiago Alexandre Pais, Ricardo Jorge Pais
BioMedInformatics.2023; 3(4): 1071. CrossRef
Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)
Mo Cheng, Xiufeng Zheng, Jing Wei, Ming Liu
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef

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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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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
Anti-Cancer Agents in Medicinal Chemistry.2025; 25(15): 1128. CrossRef
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Shuangru Chen, Liting Zhang, Jun Wang, Jiayao Lu, Ye Chen, Mingzhu Ling
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Xiali Tang, Yu Chen, Demin Jiao, Xiang Liu, Jun Chen, Yongyang Liu, Chunyan Jiang, Qingyong Chen
Anti-Cancer Agents in Medicinal Chemistry.2024; 24(1): 30. CrossRef
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Ziyang Jiang, Zhihan Gu, Xiaomin Yu, Tao Cheng, Bofu Liu
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