Cancer Research and Treatment

Original Articles

Novel Bronchoscopy Method for Molecular Profiling of Lung Cancer: Targeted Washing Technique: Mi-Hyun Kim, Hayoung Seong, Hyojin Jang, Saerom Kim, Wanho Yoo, Soo Han Kim, Jeongha Mok, Kwangha Lee, Ki Uk Kim, Min Ki Lee, Jung Seop Eom; Received November 25, 2024 Accepted February 25, 2025 Published online February 26, 2025; DOI: https://doi.org/10.4143/crt.2024.1128 [Accepted]

Abstract PDF: Purpose
There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the EGFR mutation.
Materials and Methods
A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.
Results
In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22%, 10%, and 29%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 37%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 83% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.
Conclusion
We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

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Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial: Kyoo Hyun Kim, Shinwon Hwang, Min Kyoung Kim, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Joo Hang Kim, Bhumsuk Keam, Byoung Chul Cho, So Yeon Oh, Sang Hee Cho, Sangwoo Kim, Sung-Bae Kim, Min Hee Hong, Hye Ryun Kim; Received December 11, 2024 Accepted January 27, 2025 Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.1195 [Accepted]

Purpose
The TRIUMPH trial was a biomarker-driven umbrella trial for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This analysis focuses on the PIK3CAɑ inhibitor alpelisib (arm 1) in patients with phosphoinositide 3-kinase (PI3K) pathway alterations.
Materials and Methods
Patients with PI3K pathway altered tumors were enrolled in the alpelisib arm of the TRIUMPH study. We conducted a detailed analysis of the correlation between PI3K pathway mutations and treatment outcomes including disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).
Results
From Oct 2017 and Aug 2020, 203 were enrolled, with 42 treated with alpelisib. Response evaluation was possible for 33 patients. Genomic profiles revealed PIK3CA amplifications in 26.2%, and point mutations in E542K (26.2%), E545K (23.8%), and H1047R (9.5%). Neither PIK3CA amplification nor co-occurring TP53 mutations had a notable influence on alpelisib response or survival outcomes. Although the overall response rates were similar between helical domain mutations (E542, E545) and kinase domain mutations (H1047), patients with H1047 mutations exhibited significantly poorer PFS compared to those with non-H1047 PIK3CA alterations (1.6 vs. 7.3 months, p=0.017). OS in patients with H1047 kinase domain mutations showed a trend toward being shorter compared to others, though this difference did not reach statistical significance.
Conclusion
Alpelisib showed differential efficacy based on PI3K pathway alterations in patients with R/M HNSCC and was well-tolerated. These findings suggest the usefulness of NGS testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.

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PIK3CA Mutations: Are They a Relevant Target in Adult Diffuse Gliomas?
Ana Tomás, Marta Pojo
International Journal of Molecular Sciences.2025; 26(11): 5276. CrossRef

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Review Article

The Current Evidence and Future Direction of Adjuvant Treatment for Gastric Cancer in the Era of Precision Medicine: Jong Hyuk Yun, Yoon Young Choi, Jae-Ho Cheong; Received December 18, 2024 Accepted January 22, 2025 Published online January 23, 2025; DOI: https://doi.org/10.4143/crt.2024.1222 [Epub ahead of print]

Abstract PDF PubReader ePub: Although gastric cancer remains a significant global health burden, its treatment strategies vary across different geographical regions, leading to distinct guidelines. In Asia, particularly in Korea, D2 gastrectomy followed by adjuvant chemotherapy has been established as the standard treatment for stage II/III gastric cancer based on landmark clinical trials. However, this “one-size-fits-all” approach requires refinement as emerging evidence suggests heterogeneous outcomes even within the same stage. This review discusses the evolving landscape of adjuvant treatment in gastric cancer, emphasizing the transition towards precision medicine. Recent molecular characterization of gastric cancer has revealed distinct subtypes with varying prognoses and chemotherapy responses, exemplified by the favorable outcomes of microsatellite instability–high tumors without adjuvant chemotherapy. Additionally, clinical factors including sub-stages within stage II/III, patient performance status, comorbidities, and personal preferences should be considered in treatment decisions. The integration of these molecular and clinical factors, along with shared decision-making between physicians and patients, represents a crucial step toward personalized treatment approaches. Looking ahead, the field is poised for further evolution with the emergence of immune checkpoint inhibitors, growing evidence for neoadjuvant chemotherapy in selected cases, and the potential of circulating tumor DNA as a biomarker for minimal residual disease. This comprehensive approach to treatment decision-making, considering both tumor biology and patient factors, will be essential for realizing precision medicine in gastric cancer care.

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Case Report

ALK Inhibition in a Patient with Inflammatory Myofibroblastic Tumor Harboring CARS1-ALK Fusion: Songji Choi, Miso Kim, Sheehyun Kim, Taekeun Park, Yoonjin Kwak, Jeong Mo Bae, Hongseok Yun, Jee Hyun Kim; Received December 10, 2024 Accepted December 14, 2024 Published online December 18, 2024; DOI: https://doi.org/10.4143/crt.2024.1184 [Epub ahead of print]

Abstract PDF PubReader ePub

Inflammatory myofibroblastic tumor (IMT) is a rare entity, primarily affecting young individuals, often involving the abdomen, pelvis, or lung. Approximately 50% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors a viable treatment. We report a case of a 40-year-old female with metastatic IMT harboring a CARS1-ALK fusion. Initial chemotherapy failed, but targeted therapy with alectinib through the KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study led to significant tumor regression and ongoing, durable clinical improvement of 19 months. This case highlights the importance of precision medicine and raises the reappraisal of targeted agents outside of approved indications for rare cancers with actionable genomic alterations.

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Inflammatory myofibroblastic tumors of the colon in pediatrics: clinical presentation, management, and outcomes—A case report and systematic review of literature
Ismael Elhalaby, Omar Koura, Rofyda Elhalaby, Wael Zeina, Mohamed Shareef, Essam Elhalaby
International Journal of Colorectal Disease.2025;[Epub] CrossRef

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Original Articles

Machine Learning–Based Prognostic Gene Signature for Early Triple-Negative Breast Cancer: Ju Won Kim, Jonghyun Lee, Sung Hak Lee, Sangjeong Ahn, Kyong Hwa Park; Received September 26, 2024 Accepted November 18, 2024 Published online November 19, 2024; DOI: https://doi.org/10.4143/crt.2024.937 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to develop a machine learning–based approach to identify prognostic gene signatures for early-stage triple-negative breast cancer (TNBC) using next-generation sequencing data from Asian populations.
Materials and Methods
We utilized next-generation sequencing data to analyze gene expression profiles and identify potential biomarkers. Our methodology involved integrating various machine learning techniques, including feature selection and model optimization. We employed logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curves to validate the identified gene signatures.
Results
We identified a gene signature significantly associated with relapse in TNBC patients. The predictive model demonstrated robustness and accuracy, with an area under the ROC curve of 0.9087, sensitivity of 0.8750, and specificity of 0.9231. The Kaplan-Meier survival analysis revealed a strong association between the gene signature and patient relapse, further validated by logistic regression analysis.
Conclusion
This study presents a novel machine learning-based prognostic tool for TNBC, offering significant implications for early detection and personalized treatment. The identified gene signature provides a promising approach for improving the management of TNBC, contributing to the advancement of precision oncology.

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General

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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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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Review Article

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design: Hyerim Ha, Hee Yeon Lee, Jee Hyun Kim, Do Yeun Kim, Ho Jung An, SeungJin Bae, Hye-sung Park, Jin Hyoung Kang; Cancer Res Treat. 2024;56(4):991-1013. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2024.128

Abstract PDF Supplementary Material PubReader ePub

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

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Co-Encapsulation of Multiple Antineoplastic Agents in Liposomes by Exploring Microfluidics
Sajid Asghar, Radu Iliescu, Rares-Ionut Stiufiuc, Brindusa Dragoi
International Journal of Molecular Sciences.2025; 26(8): 3820. CrossRef

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Special Article

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP: Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim; Cancer Res Treat. 2024;56(3):721-742. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.1043

Abstract PDF PubReader ePub

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

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Real-World Data: Implementation and Outcomes of Next-Generation Sequencing in the MENA Region
Rami Mahfouz, Reine Abou Zeidane, Tasnim Diab, Ali Tarhini, Eman Sbaity, Houry Kazarian, Yomna El Zibaoui, Nour Sabiha Naji, Mounir Barake, Hazem I. Assi
Diagnostics.2025; 15(10): 1183. CrossRef
Exploring PIXE Applications in Oncology: A Comprehensive Review
G. J. Naga Raju
International Journal of Advanced Research in Science, Communication and Technology.2025; : 261. CrossRef

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Original Articles

Breast cancer

Next-Generation Sequencing in Breast Cancer Patients: Real-World Data for Precision Medicine: Hyunwoo Lee, Yoon Ah Cho, Deok Geun Kim, Eun Yoon Cho; Cancer Res Treat. 2024;56(1):149-161. Published online August 11, 2023; DOI: https://doi.org/10.4143/crt.2023.800

Abstract PDF Supplementary Material PubReader ePub

Purpose
Breast cancer is one of the most common causes of cancer-related death in females. Numerous drug-targetable biomarkers and predictive biomarkers have been developed. Some researchers have expressed doubts about the need for next-generation sequencing (NGS) studies in daily practice. This study analyzed the results of NGS studies on breast cancer at a single institute and evaluated the real-world applications of NGS data to precision medicine for breast cancer.
Materials and Methods
We retrospectively collected the results of NGS studies and analyzed the histopathologic features and genetic profiles of patients treated for breast cancer from 2010 to 2021. Seventy cases had data from CancerSCAN, a customized panel of 375 cancer-associated genes, and 110 cases had data from TruSight Oncology 500.
Results
The most frequently detected single nucleotide variant was the TP53 mutation (123/180, 68.3%), followed by PIK3CA mutations (51/180, 28.3%). Estrogen receptor 1 (ESR1) mutation was detected in 11 patients (6.1%), of whom 10 had hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer, and two had no history of prior endocrine therapy. Based on their NGS study results, 13 patients (7.2%) received target therapy. Among them, four patients had a BRCA1 or BRCA2 germline mutation, and nine patients had a PIK3CA mutation.
Conclusion
NGS can provide information about predictive biomarkers and drug-targetable biomarkers that can enable treatment and participation in clinical trials based on precision medicine. Further studies should be conducted to excavate novel drug-targetable biomarkers and develop additional target therapies.

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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,
Cancer Research and Treatment.2025; 57(2): 443. CrossRef
Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
Pathology.2024; 56(5): 653. CrossRef
Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer
Elena Guerini-Rocco, Konstantinos Venetis, Giulia Cursano, Eltjona Mane, Chiara Frascarelli, Francesco Pepe, Mariachiara Negrelli, Edoardo Olmeda, Davide Vacirca, Alberto Ranghiero, Dario Trapani, Carmen Criscitiello, Giuseppe Curigliano, Christian Rolfo,
Critical Reviews in Oncology/Hematology.2024; 201: 104427. CrossRef
An ultra-sensitive and rapid immunosensor for the onsite detection of circulating tumor DNA in breast cancer
Yi Bi, Xiao Lv, Ke Wang, Jinyu Wu, Xiang Shi, Xiaodong Zheng, Xiaogang Lin
Frontiers in Bioengineering and Biotechnology.2024;[Epub] CrossRef
NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2–G3 breast cancer
Carmen Maria Ardeleanu, Maria Victoria Olinca , Cristian Gabriel Viişoreanu , Horaţiu Alin Mureşan , Adriana Tecuceanu-Vulpe , Georgiana Manole , Iulia Elena Gune , Bianca Gălăţeanu , Andreea-Corina Ilie-Petrov
Romanian Journal of Morphology and Embryology.2024; 65(2): 195. CrossRef

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Head and Neck cancer

A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial: Kyoo Hyun Kim, Sun Min Lim, Hee Kyung Ahn, Yun-Gyoo Lee, Keun-Wook Lee, Myung-Ju Ahn, Bhumsuk Keam, Hye Ryun Kim, Hyun Woo Lee, Ho Jung An, Jin-Soo Kim; Cancer Res Treat. 2024;56(1):37-47. Published online July 20, 2023; DOI: https://doi.org/10.4143/crt.2023.433

Abstract PDF PubReader ePub

Purpose
Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial.
Materials and Methods
The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis.
Results
Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable.
Conclusion
Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

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Targeting fibroblast growth factor receptor (FGFR) with inhibitors in head and neck cancers: Their roles, mechanisms and challenges
Daowen Luo, Sirinart Kumfu, Nipon Chattipakorn, Siriporn C. Chattipakorn
Biochemical Pharmacology.2025; 235: 116845. CrossRef
One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents
Michael Atef Fawzy, Karim Hagag Ibrahim, Ashraf A Aly, Asmaa H Mohamed, Sara Mohamed Naguib Abdel Hafez, Walaa Yehia Abdelzaher, Eslam B Elkaeed, Aisha A Alsfouk, El-Shimaa MN Abdelhafez
Future Medicinal Chemistry.2024; 16(21): 2211. CrossRef
Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck
Prashant Puttagunta, Saagar V. Pamulapati, James E. Bates, Jennifer H. Gross, William A. Stokes, Nicole C. Schmitt, Conor Steuer, Yong Teng, Nabil F. Saba
Frontiers in Oncology.2023;[Epub] CrossRef

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Case Report

Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA: Jung-Ki Yoon, Jongseong Ahn, Sheehyun Kim, Hwang-Phil Kim, Jun-kyu Kang, Duhee Bang, Yoojoo Lim, Tae-You Kim; Cancer Res Treat. 2023;55(3):1048-1052. Published online January 31, 2023; DOI: https://doi.org/10.4143/crt.2022.1529

Abstract PDF Supplementary Material PubReader ePub

Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446*)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cell-free DNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446*) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy.

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Circulating tumor DNA validity and potential uses in metastatic breast cancer
Ottavia Amato, Nefeli Giannopoulou, Michail Ignatiadis
npj Breast Cancer.2024;[Epub] CrossRef
DNA damage targeted therapy for advanced breast cancer
Vanessa Patel, Sandra Casimiro, Catarina Abreu, Tiago Barroso, Rita Teixeira de Sousa, Sofia Torres, Leonor Abreu Ribeiro, Gonçalo Nogueira-Costa, Helena Luna Pais, Conceição Pinto, Leila Costa, Luís Costa
Exploration of Targeted Anti-tumor Therapy.2024; 5(3): 678. CrossRef
Practical Utility of Liquid Biopsies for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer
Seung-Hwan Jeong, Dongsoo Kyung, Hyeong Dong Yuk, Chang Wook Jeong, Wookjae Lee, Jung-Ki Yoon, Hwang-Phill Kim, Duhee Bang, Tae-You Kim, Yoojoo Lim, Cheol Kwak
Cancers.2023; 15(10): 2847. CrossRef

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Special Article

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group: Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim; Cancer Res Treat. 2022;54(1):1-9. Published online December 13, 2021; DOI: https://doi.org/10.4143/crt.2021.1115; Correction in: Cancer Res Treat 2023;55(3):1061

Abstract PDF PubReader ePub

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

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Clinical implementation of next-generation sequencing testing and genomically-matched therapy: a real-world data in a tertiary hospital
Jin Won Kim, Hee Young Na, Sejoon Lee, Ji-Won Kim, Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jong Seok Lee, Jaihwan Kim, Jin-Hyeok Hwang, Kihwan Hwang, Chae-Yong Kim, Yong Beom Kim, Soomin Ahn, Kyu Sang Lee, Hyojin Kim, Hye Seung Lee, So Yeo
Scientific Reports.2025;[Epub] CrossRef
Expert Consensus on Molecular Tumor Boards in Taiwan: Joint Position Paper by the Taiwan Oncology Society and the Taiwan Society of Pathology
Ming-Huang Chen, Wan-Shan Li, Bin-Chi Liao, Chiao-En Wu, Chien-Feng Li, Chia-Hsun Hsieh, Feng-Che Kuan, Huey-En Tzeng, Jen-Fan Hang, Nai-Jung Chiang, Tse-Ching Chen, Tom Wei-Wu Chen, John Wen-Cheng Chang, Yao-Yu Hsieh, Yen-Lin Chen, Yi-Chen Yeh, Yi-Hsin L
Journal of Cancer Research and Practice.2024;[Epub] CrossRef
Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II
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Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
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Nationwide precision oncology pilot study: KOrean Precision Medicine Networking Group Study of MOlecular profiling-guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) KCSG AL-20-05
T.-Y. Kim, S.Y. Kim, J.H. Kim, H.A. Jung, Y.J. Choi, I.G. Hwang, Y. Cha, G.-W. Lee, Y.-G. Lee, T.M. Kim, S.-H. Lee, S. Lee, H. Yun, Y.L. Choi, S. Yoon, S.W. Han, T.-Y. Kim, T.W. Kim, D.Y. Zang, J.H. Kang
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International Journal of Cancer.2023; 153(3): 571. CrossRef
Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists
Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee
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Implementation of Precision Oncology in the National Healthcare System: A Statement Proposal Endorsed by Italian Scientific Societies
Gianpiero Fasola, Maria C. Barducci, Valeria D. Tozzi, Luigi Cavanna, Saverio Cinieri, Francesco Perrone, Carmine Pinto, Antonio Russo, Anna Sapino, Francesco Grossi, Giuseppe Aprile
JCO Precision Oncology.2023;[Epub] CrossRef
Development of two 410-cancer-gene panel tests for solid tumors and liquid biopsy based on genome data of 5,143 Japanese cancer patients
Yuji SHIMODA, Takeshi NAGASHIMA, Kenichi URAKAMI, Fukumi KAMADA, Sou NAKATANI, Maki MIZUGUCHI, Masakuni SERIZAWA, Keiichi HATAKEYAMA, Keiichi OHSHIMA, Tohru MOCHIZUKI, Sumiko OHNAMI, Shumpei OHNAMI, Takeshi KAWAKAMI, Kentaro YAMAZAKI, Haruyasu MURAKAMI, H
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Clinical Implication of Molecular Tumor Board
Soohyeon Lee
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Somatic Mutations of TP53 Identified by Targeted Next-Generation Sequencing Are Poor Prognostic Factors for Primary Operable Breast Cancer: A Single-Center Study
Jung Ho Park, Mi Jung Kwon, Jinwon Seo, Ho Young Kim, Soo Kee Min, Lee Su Kim
Journal of Breast Cancer.2022; 25(5): 379. CrossRef

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Original Articles

General

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations: Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Seungtaek Lim, Sung Shim Cho, Jang Ho Cho, Sang Won Shin, Kyong Hwa Park, Yeul Hong Kim; Cancer Res Treat. 2022;54(1):30-39. Published online May 20, 2021; DOI: https://doi.org/10.4143/crt.2021.218

Abstract PDF PubReader ePub

Purpose
K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.
Materials and Methods
Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).
Results
In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.
Conclusion
The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Citations

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Genomic Profiling of Driver Gene Alterations in Patients With Non–Small Cell Lung Cancer, Patterns of Treatment and Impact on Survival Outcomes: A Single Center Experience of More Than 1200 Patients
Minit Shah, Vanita Noronha, Vijay Patil, Ajay Kumar Singh, Nandini Menon, Supriya Goud, Srushti Shah, Sucheta More, Akhil Kapoor, Bal Krishna Mishra, Pratik Chandrani, Anuradha Chougule, Vinod Gupta, Priyanka Pange, Omshree Shetty, Trupti Pai, Rajiv Kaush
Clinical Lung Cancer.2025; 26(4): e270. CrossRef
Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
BMC Cancer.2024;[Epub] CrossRef
Supporting Biomarker-Driven Therapies in Oncology: A Genomic Testing Cost Calculator
Albrecht Stenzinger, Brian Cuffel, Noman Paracha, Eric Vail, Jesus Garcia-Foncillas, Clifford Goodman, Ulrik Lassen, Gilles Vassal, Sean D Sullivan
The Oncologist.2023; 28(5): e242. CrossRef
Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Scientific Reports.2023;[Epub] CrossRef
Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
Cancer Research and Treatment.2022; 54(1): 1. CrossRef

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Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas: Hyemi Shin, Jason K. Sa, Joon Seol Bae, Harim Koo, Seonwhee Jin, Hee Jin Cho, Seung Won Choi, Jong Min Kyoung, Ja Yeon Kim, Yun Jee Seo, Je-Gun Joung, Nayoung K. D. Kim, Dae-Soon Son, Jongsuk Chung, Taeseob Lee, Doo-Sik Kong, Jung Won Choi, Ho Jun Seol, Jung-Il Lee, Yeon-Lim Suh, Woong-Yang Park, Do-Hyun Nam; Cancer Res Treat. 2020;52(1):41-50. Published online May 7, 2019; DOI: https://doi.org/10.4143/crt.2019.036

Abstract PDF Supplementary Material PubReader ePub

Purpose
Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas.
Materials and Methods
To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization.
Results
Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene.
Conclusion
We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

Citations

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Comparative genomic landscape of lower-grade glioma and glioblastoma
Xinxin Sun, Qingbin Jia, Kun Li, Conghui Tian, Lili Yi, Lili Yan, Juan Zheng, Xiaodong Jia, Mingliang Gu, Michael C. Burger
PLOS ONE.2024; 19(8): e0309536. CrossRef
Actionable molecular alterations in newly diagnosed and recurrent IDH1/2 wild-type glioblastoma patients and therapeutic implications: a large mono-institutional experience using extensive next-generation sequencing analysis
Marta Padovan, Marta Maccari, Alberto Bosio, Chiara De Toni, Salvatore Vizzaccaro, Ilaria Cestonaro, Martina Corrà, Mario Caccese, Giulia Cerretti, Vittorina Zagonel, Giuseppe Lombardi
European Journal of Cancer.2023; 191: 112959. CrossRef
GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses
Zigui Chen, Dandan Zheng, Ziren Lin, Chunyuan Zhang, Cheng Wei, Xiandong Deng, Peng Yan, Chuanhua Zheng, Chuanliu Lan, Chengjian Qin, Xuanlei Wei, Deling Qin, Yongfang Wu, Jun Peng, Changfeng Miao, Liuxue Lu, Ying Xia, Qisheng Luo
Frontiers in Immunology.2023;[Epub] CrossRef
Comprehensive clinical assays for molecular diagnostics of gliomas: the current state and future prospects
Alina Penkova, Olga Kuziakova, Valeriia Gulaia, Vladlena Tiasto, Nikolay V. Goncharov, Daria Lanskikh, Valeriia Zhmenia, Ivan Baklanov, Vladislav Farniev, Vadim Kumeiko
Frontiers in Molecular Biosciences.2023;[Epub] CrossRef
A rapid, multiplex digital PCR assay to detect gene variants and fusions in non‐small cell lung cancer
Bryan Leatham, Katie McNall, Hari K. K. Subramanian, Lucien Jacky, John Alvarado, Dominic Yurk, Mimi Wang, Donald C. Green, Gregory J. Tsongalis, Aditya Rajagopal, Jerrod J. Schwartz
Molecular Oncology.2023; 17(11): 2221. CrossRef
Next generation sequencing in adult patients with glioblastoma in Switzerland: a multi-centre decision analysis
A. M. Zeitlberger, P. M. Putora, S. Hofer, P. Schucht, D. Migliorini, A. F. Hottinger, U. Roelcke, H. Läubli, P. Spina, O. Bozinov, M. Weller, M. C. Neidert, T. Hundsberger
Journal of Neuro-Oncology.2022; 158(3): 359. CrossRef
Targeted next‐generation sequencing of adult gliomas for retrospective prognostic evaluation and up‐front diagnostics
J. K. Petersen, H. B. Boldt, M. D. Sørensen, S. Blach, R. H. Dahlrot, S. Hansen, M. Burton, M. Thomassen, T. Kruse, F. R. Poulsen, L. Andreasen, H. Hager, B. P. Ulhøi, S. Lukacova, G. Reifenberger, B. W. Kristensen
Neuropathology and Applied Neurobiology.2021; 47(1): 108. CrossRef
Development of MR-based preoperative nomograms predicting DNA copy number subtype in lower grade gliomas with prognostic implication
Siwei Zhang, Shanshan Wu, Yun Wan, Yongsong Ye, Ying Zhang, Zelan Ma, Quanlan Guo, Hongdan Zhang, Li Xu
European Radiology.2021; 31(4): 2094. CrossRef
Comprehensive Molecular Characterization of Chinese Patients with Glioma by Extensive Next-Generation Sequencing Panel Analysis
Chun Zeng, Jing Wang, Mingwei Li, Huina Wang, Feng Lou, Shanbo Cao, Changyu Lu
Cancer Management and Research.2021; Volume 13: 3573. CrossRef
Analyzing Genetic Differences Between Sporadic Primary and Secondary/Tertiary Hyperparathyroidism by Targeted Next-Generation Panel Sequencing
Yu Ah Hong, Ki Cheol Park, Bong Kyun Kim, Jina Lee, Woo Young Sun, Hae Joung Sul, Kyung-Ah Hwang, Won Jung Choi, Yoon-Kyung Chang, Suk Young Kim, Soyoung Shin, Joonhong Park
Endocrine Pathology.2021; 32(4): 501. CrossRef
Multisite verification of the accuracy of a multi-gene next generation sequencing panel for detection of mutations and copy number alterations in solid tumours
John Bartlett, Yutaka Amemiya, Heleen Arts, Jane Bayani, Barry Eng, Daria Grafodatskaya, Suzanne Kamel Reid, Mathieu Lariviere, Bryan Lo, Rebecca McClure, Vinay Mittal, Bekim Sadikovic, Seth Sadis, Arun Seth, Jeff Smith, Xiao Zhang, Harriet Feilotter, Alv
PLOS ONE.2021; 16(10): e0258188. CrossRef
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Ching-Yuan Wang, Yen-An Tang, I-Wen Lee, Fong-Ming Chang, Chun-Wei Chien, Hsien-An Pan, H. Sunny Sun
BMC Medical Genomics.2021;[Epub] CrossRef
Therapeutic Efficacy of GC1118, a Novel Anti-EGFR Antibody, against Glioblastoma with High EGFR Amplification in Patient-Derived Xenografts
Kyoungmin Lee, Harim Koo, Yejin Kim, Donggeon Kim, Eunju Son, Heekyoung Yang, Yangmi Lim, Minkyu Hur, Hye Won Lee, Seung Won Choi, Do-Hyun Nam
Cancers.2020; 12(11): 3210. CrossRef

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Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients: Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park; Cancer Res Treat. 2019;51(1):211-222. Published online April 23, 2018; DOI: https://doi.org/10.4143/crt.2018.132

Abstract PDF Supplementary Material PubReader ePub

Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Clinical implementation of next-generation sequencing testing and genomically-matched therapy: a real-world data in a tertiary hospital
Jin Won Kim, Hee Young Na, Sejoon Lee, Ji-Won Kim, Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jong Seok Lee, Jaihwan Kim, Jin-Hyeok Hwang, Kihwan Hwang, Chae-Yong Kim, Yong Beom Kim, Soomin Ahn, Kyu Sang Lee, Hyojin Kim, Hye Seung Lee, So Yeo
Scientific Reports.2025;[Epub] CrossRef
Real-World Data and Clinical Implications of Next-Generation Sequencing (NGS)-Based Analysis in Metastatic Breast Cancer Patients
Fabio Canino, Antonio Tornincasa, Stefania Bettelli, Samantha Manfredini, Monica Barbolini, Luca Moscetti, Claudia Omarini, Angela Toss, Fabio Tamburrano, Giuseppina Antonelli, Federica Baglio, Lorenzo Belluzzi, Giulio Martinelli, Salvatore Natalizio, Orn
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Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists
Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee
Journal of Pathology and Translational Medicine.2023; 57(5): 265. CrossRef
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IC Uzoma, IA Taiwo, NI Ugwu, MA Durosinmi, O Akinloye
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Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
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Gelareh Sadigh, Hilary Gee Goeckner, Ella A. Kazerooni, Bruce E. Johnson, Robert A. Smith, Devon V. Adams, Ruth C. Carlos
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Clinical Application of Next-Generation Sequencing in Patients With Breast Cancer: Real-World Data
Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Heechul Shin, Eunyoung Kang, Eun-Kyu Kim, Sejoon Lee, Ji Won Woo, Hee Young Na, Soomin Ahn, Bum-Sup Jang, In Ah Kim, So Yeon Park, Jee Hyun Kim
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Birgitta I. Hiddinga, Klaas Kok
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Jwa Hoon Kim, Shinkyo Yoon, Dae Ho Lee, Se Jin Jang, Sung‐Min Chun, Sang‐We Kim
Cancer Medicine.2021; 10(10): 3197. CrossRef
Actionability evaluation of biliary tract cancer by genome transcriptome analysis and Asian cancer knowledgebase
Yuki Okawa, Nobutaka Ebata, Nayoung K.D. Kim, Masashi Fujita, Kazuhiro Maejima, Shota Sasagawa, Toru Nakamura, Woong-Yang Park, Satoshi Hirano, Hidewaki Nakagawa
Oncotarget.2021; 12(15): 1540. CrossRef
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Byung-Joo Min, Woo Seung Lee, Myung-Eui Seo, Kye-Hwa Lee, Seung-Yong Jeong, Ja-Lok Ku, Yeul Hong Kim, Sang-Won Shin, Ju Han Kim
Cancers.2021; 13(20): 5112. CrossRef
Junction Location Identifier (JuLI)
Hyun-Tae Shin, Nayoung K.D. Kim, Jae Won Yun, Boram Lee, Sungkyu Kyung, Ki-Wook Lee, Daeun Ryu, Jinho Kim, Joon Seol Bae, Donghyun Park, Yoon-La Choi, Se-Hoon Lee, Myung-Ju Ahn, Keunchil Park, Woong-Yang Park
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Breast Cancer Research and Treatment.2020; 182(2): 491. CrossRef

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Omic Approach in Non-smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine: Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti; Cancer Res Treat. 2018;50(2):356-365. Published online May 26, 2017; DOI: https://doi.org/10.4143/crt.2017.125

Abstract PDF Supplementary Material PubReader ePub

Purpose
Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease.
Materials and Methods
A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients’ peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants.
Results
Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR.
Conclusion
In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.

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Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies: Eun Jin Heo, Young Jae Cho, William Chi Cho, Ji Eun Hong, Hye-Kyung Jeon, Doo-Yi Oh, Yoon-La Choi, Sang Yong Song, Jung-Joo Choi, Duk-Soo Bae, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Woong-Yang Park, Byoung-Gie Kim, Jeong-Won Lee; Cancer Res Treat. 2017;49(4):915-926. Published online January 4, 2017; DOI: https://doi.org/10.4143/crt.2016.322

Abstract PDF Supplementary Material PubReader ePub

Purpose
Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.
Materials and Methods
We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.
Results
Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor–overexpressing PDX with clear cell histology (p=0.023).
Conclusion
PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.

Citations

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