Cancer Research and Treatment

Original Articles

Longitudinal Circulating Tumor DNA Profiling as a Biomarker for Response and Resistance in Platinum-Refractory Head and Neck Squamous Cell Carcinoma: Wonyoung Choi, Jong-Ho Lee, Junsun Ryu, Sung Weon Choi, Yuh-Seog Jung, Joo-Yong Park, Chang Hwan Ryu, Sung Yong Choi, Weon Seo Park, Sun-Young Kong, Tak Yun; Received October 5, 2025 Accepted November 3, 2025 Published online November 4, 2025; DOI: https://doi.org/10.4143/crt.2025.1089 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
Immune checkpoint inhibitors (ICIs) are the standard treatment for platinum-refractory head and neck squamous cell carcinoma (HNSCC). This study aimed to characterize genomic alterations, monitor dynamic changes in circulating tumor DNA (ctDNA) associated with treatment response, and identify novel alterations linked to resistance through serial ctDNA profiling.
Materials and Methods
Patients with platinum-refractory HNSCC receiving nivolumab were enrolled. ctDNA was analyzed using FoundationOne Liquid CDx at baseline, 6 weeks after treatment, and at disease progression.
Results
A total of 36 patients were enrolled, and 33 were evaluable for ctDNA. The most frequent baseline alterations were TP53 (75.8%), followed by TERT (27.3%), NOTCH1 (24.2%), CDKN2A (12.1%), and CCND1 (12.1%). Of 27 patients with measurable lesions, five achieved a partial response with a response rate of 18.5%. Dynamic ctDNA profiling revealed all responders had marked reductions in both the sum of variant allele frequencies (sumVAF) and the maximum variant allele frequencies (maxVAF) across detected mutations. A decrease in sumVAF or maxVAF correlated with longer treatment durations, and patients with a > 50% decrease in either sumVAF or maxVAF showed significantly longer progression-free survival. Additionally, serial profiling identified de novo mutations in 17 patients, detected during stable disease or progression.
Conclusion
Serial ctDNA analysis provides a noninvasive tool for monitoring treatment response and detecting emerging resistance in HNSCC treated with ICIs. A significant reduction in ctDNA at 6 weeks was associated with improved clinical outcomes and warrants validation in larger, prospective studies to define its role as a predictive biomarker in HNSCC.

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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
Description of six cases of melanoma in 512 patients with germline pathogenic variants in the TP53 gene
Elisabeth de A. C. Callegaro, Janina Pontes Pisani, Vanessa Monteleone, Maria Isabel Achatz
Familial Cancer.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

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General

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients: Wonyoung Choi, Yun-Hee Kim, Sang Myung Woo, Yebeen Yu, Mi Rim Lee, Woo Jin Lee, Jung Won Chun, Sung Hoon Sim, Heejung Chae, Hyoeun Shim, Keun Seok Lee, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1077-1086. Published online June 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1630

Abstract PDF Supplementary Material PubReader ePub

Purpose
Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.
Materials and Methods
Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.
Results
We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients.
Conclusion
Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Citations

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Lung Cancer

The Clinical Impact of Capmatinib in the Treatment of Advanced Non–Small Cell Lung Cancer with MET Exon 14 Skipping Mutation or Gene Amplification: Wonyoung Choi, Seog-Yun Park, Youngjoo Lee, Kun Young Lim, Minjoung Park, Geon Kook Lee, Ji-Youn Han; Cancer Res Treat. 2021;53(4):1024-1032. Published online January 29, 2021; DOI: https://doi.org/10.4143/crt.2020.1331

Abstract PDF Supplementary Material PubReader ePub

Purpose
Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non–small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification.
Materials and Methods
Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients’ clinical outcome were retrospectively reviewed.
Results
A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123).
Conclusion
Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.

Citations

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Exploratory Identification of Gene Copy Number Cut-Off for NGS-Based MET Amplification Assessment and Clinical Relevance to MET Inhibitor Outcomes in Non-Small-Cell Lung Cancer
Si-Yang Liu, Zhi Xie, Lixu Yan, Guang-Ling Jie, Jia-Yi Deng, Qingling Zhang, Zhan Huang, Jin Wang, Zhou Zhang, Yang Shao, Hao Meng, Yan Zhang, Xu-Chao Zhang, Hua-Jun Chen, Wen-Zhao Zhong, Qing Zhou, Yi-Long Wu
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Caiyu Jiang, Shenglong Xie, Kegang Jia, Gang Feng, Xudong Ren, Youyu Wang
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Michael Abele, Anton Karelin, Michaela Pogoda, Ulrike Faust, Sorin Armeanu-Ebinger, Jakob Admard, Alexandra Liebmann, Irina Bonzheim, Nicolas Waespe, Margo Hoover-Regan, Andreas Block, Martin Reck, Ewa Bien, Malgorzata Krawczyk, Dominik T. Schneider, Step
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Ann-Katrin Piper, Chelsea Penney, Jacqueline Holliday, Gary Tincknell, Yafeng Ma, Sarbar Napaki, Klaus Pantel, Daniel Brungs, Marie Ranson
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Hang Zhang, Yingying Zhang, Yingying Zhu, Tian Dong, Zheng Liu
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Synthesis and bioassay of 3-Aryl -1-(pyridin-4-yl)benzo[4,5]imidazo[1,2-d][1,2,4]- triazin-4(3H)-ones as anti-cancer agents
Bassam Abu Thaher, Ihab Al-Masri, Kanan Wahedy, Rami Morjan, Saeb Aliwaini, Iman Mahmoud Al atter, Aayat Ahmed Elmabhouh, Areej khaled AL ibwaini, Saba Luay Alkhaldi, Basem Qeshta, Claus Jacob, Hans-Peter Deigner
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Yueren Yan, Yunpeng Ren, Yufang Bao, Yongbo Wang
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Clinicopathological characteristics of Non-Small Cell Lung Cancer (NSCLC) patients with c-MET exon 14 skipping mutation, MET overexpression and amplification
Caixia Ding, Yanyi Qiu, Juan Zhang, Wei Wei, Hongbian Gao, Yong Yuan, Xiaomin Wang
BMC Pulmonary Medicine.2023;[Epub] CrossRef
Long-Term Efficacy, Safety, and Subgroup Analysis of Savolitinib in Chinese Patients With NSCLCs Harboring MET Exon 14 Skipping Alterations
Shun Lu, Jian Fang, Xingya Li, Lejie Cao, Jianying Zhou, Qisen Guo, Zongan Liang, Ying Cheng, Liyan Jiang, Nong Yang, Zhigang Han, Jianhua Shi, Yuan Chen, Hua Xu, Helong Zhang, Gongyan Chen, Rui Ma, Sanyuan Sun, Yun Fan, Songhua Fan, Jie Yu, Puhan Lu, Xia
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Bo Mi Ku, Sungwon Park, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Yoon-La Choi, Myung-Ju Ahn
Precision and Future Medicine.2022; 6(4): 233. CrossRef
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Matthew Z Guo, Kristen A Marrone, Alexander Spira, David M Waterhouse, Susan C Scott
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Immunogenicity and Optimal Timing of 13-Valent Pneumococcal Conjugate Vaccination during Adjuvant Chemotherapy in Gastric and Colorectal Cancer: A Randomized Controlled Trial: Wonyoung Choi, Jong Gwang Kim, Seung-Hoon Beom, Jun-Eul Hwang, Hyun-Jung Shim, Sang-Hee Cho, Min-Ho Shin, Sin-Ho Jung, Ik-Joo Chung, Joon Young Song, Woo Kyun Bae; Cancer Res Treat. 2020;52(1):246-253. Published online July 9, 2019; DOI: https://doi.org/10.4143/crt.2019.189

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pneumococcal vaccination (13-valent pneumococcal conjugate vaccine [PCV13]) is recommended to cancer patients undergoing systemic chemotherapy. However, the optimal time interval between vaccine administration and initiation of chemotherapy has been little studied in adult patients with solid malignancies.
Materials and Methods
We conducted a prospective randomized controlled trial to evaluate whether administering PCV13 on the first day of chemotherapy is non-inferior to vaccinating 2 weeks prior to chemotherapy initiation. Patients were randomly assigned to two study arms, and serum samples were collected at baseline and 4 weeks after vaccination to analyze the serologic response against Streptococcus pneumoniae using a multiplexed opsonophagocytic killing assay.
Results
Of the 92 patients who underwent randomization, 43 patients in arm A (vaccination 2 weeks before chemotherapy) and 44 patients in arm B (vaccination on the first day of chemotherapy) were analyzed. Immunogenicity was assessed by geometric mean and fold-increase of post-vaccination titers, seroprotection rates (percentage of patients with post-vaccination titers > 1:64), and seroconversion rates (percentage of patients with > 4-fold increase in post-vaccination titers). Serologic responses to PCV13 did not differ significantly between the two study arms according to all three types of assessments.
Conclusion
The overall antibody response to PCV13 is adequate in patients with gastric and colorectal cancer during adjuvant chemotherapy, and no significant difference was found when patients were vaccinated two weeks before or on the day of chemotherapy initiation.

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