Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection: Dong-Hoon Lim, Hyunseok Yoon, Kyu-pyo Kim, Baek-Yeol Ryoo, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Song Cheol Kim, Seung-Mo Hong, Jaewon Hyung, Changhoon Yoo; Cancer Res Treat. 2023;55(4):1313-1320. Published online May 4, 2023; DOI: https://doi.org/10.4143/crt.2023.452

Abstract PDF Supplementary Material PubReader ePub

Purpose
There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods
Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Results
Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Conclusion
Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Citations

Citations to this article as recorded by

A Review of Circulating Tumor DNA (ctDNA) in Pancreatic Cancer: Ready for the Clinic?
Purvi Jonnalagadda, Virginia Arnold, Benjamin A. Weinberg
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
A Practical Approach to Interpreting Circulating Tumor DNA in the Management of Gastrointestinal Cancers
Zexi Allan, David S Liu, Margaret M Lee, Jeanne Tie, Nicholas J Clemons
Clinical Chemistry.2024; 70(1): 49. CrossRef
High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study
Lei Huang, Yao Lv, Shasha Guan, Huan Yan, Lu Han, Zhikuan Wang, Quanli Han, Guanghai Dai, Yan Shi
Journal of Translational Medicine.2024;[Epub] CrossRef
Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies
Khadija Turabi, Kelsey Klute, Prakash Radhakrishnan
Cancers.2024; 16(13): 2432. CrossRef
Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma
Ibone Labiano, Ana E. Huerta, Maria Alsina, Hugo Arasanz, Natalia Castro, Saioa Mendaza, Arturo Lecumberri, Iranzu Gonzalez-Borja, David Guerrero-Setas, Ana Patiño-Garcia, Gorka Alkorta-Aranburu, Irene Hernández-Garcia, Virginia Arrazubi, Elena Mata, Davi
Scientific Reports.2024;[Epub] CrossRef
Liquid biopsy analysis of lipometabolic exosomes in pancreatic cancer
Wei Guo, Peiyao Ying, Ruiyang Ma, Zuoqian Jing, Gang Ma, Jin Long, Guichen Li, Zhe Liu
Cytokine & Growth Factor Reviews.2023; 73: 69. CrossRef

4,168 View
264 Download
5 Web of Science
6 Crossref

Gynecologic cancer

Genomic Correlates of Unfavorable Outcome in Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemoradiation: Yuchun Wei, Chuqing Wei, Liang Chen, Ning Liu, Qiuxiang Ou, Jiani C. Yin, Jiaohui Pang, Zhenhao Fang, Xue Wu, Xiaonan Wang, Dianbin Mu, Yang Shao, Jinming Yu, Shuanghu Yuan; Cancer Res Treat. 2022;54(4):1209-1218. Published online January 17, 2022; DOI: https://doi.org/10.4143/crt.2021.963

Abstract PDF Supplementary Material PubReader ePub

Purpose
Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer.
Materials and Methods
A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits.
Results
Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse.
Conclusion
We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Citations

Citations to this article as recorded by

Comprehensive characterization of PKHD1 mutation in human colon cancer
Lu Han, Fangming Gong, Xuxiaochen Wu, Wanxiangfu Tang, Hua Bao, Yue Wang, Daizhenru Wang, Yulan Sun, Peng Li
Cancer Medicine.2024;[Epub] CrossRef
PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer
Wenhan Li, Yuhui Huang, Man Xiao, Jing Zhao, Shi Du, Zehua Wang, Sha Hu, Lu Yang, Jing Cai
iScience.2024; 27(3): 109160. CrossRef
Comprehensive genomic profiling of pulmonary spindle cell carcinoma using tissue and plasma samples: insights from a real‐world cohort analysis
Yi Sun, Shilei Qin, Song Wang, Jiaohui Pang, Qiuxiang Ou, Weiquan Liang, Hai Zhong
The Journal of Pathology: Clinical Research.2024;[Epub] CrossRef
PD-1 inhibitor plus concurrent chemoradiotherapy for high-risk locally advanced cervical cancer
Cong Wang, Lijun Liu, Xia Li, Jia Lei, Yiqian Li, Zhibo Shen, Huirong Shi, Yan Cheng
Future Oncology.2024; 20(20): 1415. CrossRef
A biomarker exploration in small-cell lung cancer for brain metastases risk and prophylactic cranial irradiation therapy efficacy
Li Li, Ning Liu, Tao Zhou, Xueting Qin, Xiaoyu Song, Song Wang, Jiaohui Pang, Qiuxiang Ou, Yong Wang, Dexian Zhang, Jiaran Li, Fuhao Xu, Shuming Shi, Jinming Yu, Shuanghu Yuan
Lung Cancer.2024; 196: 107959. CrossRef
Prospects of POLD1 in Human Cancers: A Review
Michał Gola, Przemysław Stefaniak, Janusz Godlewski, Barbara Jereczek-Fossa, Anna Starzyńska
Cancers.2023; 15(6): 1905. CrossRef
Copy-number-gain of telomerase reverse transcriptase (hTERT) is associated with an unfavorable prognosis in esophageal adenocarcinoma
Su Ir Lyu, Felix C. Popp, Adrian Georg Simon, Anne Maria Schultheis, Thomas Zander, Caroline Fretter, Wolfgang Schröder, Christiane J. Bruns, Thomas Schmidt, Alexander Quaas, Karl Knipper
Scientific Reports.2023;[Epub] CrossRef

7,688 View
175 Download
7 Web of Science
7 Crossref

General

Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing: Hai-Yun Wang, Ling Deng, Ying-Qing Li, Xiao Zhang, Ya-Kang Long, Xu Zhang, Yan-Fen Feng, Yuan He, Tao Tang, Xin-Hua Yang, Fang Wang; Cancer Res Treat. 2021;53(4):973-982. Published online February 18, 2021; DOI: https://doi.org/10.4143/crt.2020.798

Abstract PDF Supplementary Material PubReader ePub

Purpose
Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice.
Materials and Methods
TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate.
Results
The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs.
Conclusion
Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

Citations

Citations to this article as recorded by

Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study
Ling Deng, Hai‐Yun Wang, Chun‐Fang Hu, Xiao‐Yun Liu, Kuntai Jiang, Juan‐Juan Yong, Xiao‐Yan Wu, Kai‐Hua Guo, Fang Wang
Pigment Cell & Melanoma Research.2024; 37(3): 363. CrossRef
Genomic Features of Homologous Recombination Deficiency in Breast Cancer: Impact on Testing and Immunotherapy
Umer Ali, Sunitha Vungarala, Venkataswarup Tiriveedhi
Genes.2024; 15(2): 162. CrossRef
Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
Clinical and Experimental Medicine.2024;[Epub] CrossRef
Clinical significance of genetic profiling based on different anatomic sites in patients with mucosal melanoma who received or did not receive immune checkpoint inhibitors
Hai-Yun Wang, Ye Liu, Ling Deng, Kuntai Jiang, Xin-Hua Yang, Xiao-Yan Wu, Kai-Hua Guo, Fang Wang
Cancer Cell International.2023;[Epub] CrossRef
Homologous recombination repair gene mutations as a predictive biomarker for immunotherapy in patients with advanced melanoma
Zhixuan You, Meng Lv, Xuanyu He, Yingqin Pan, Junfeng Ge, Xue Hu, Yating Zheng, Mengli Huang, Chengzhi Zhou, Changxuan You
Frontiers in Immunology.2022;[Epub] CrossRef
The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy
Congqi Shi, Kaiyu Qin, Anqi Lin, Aimin Jiang, Quan Cheng, Zaoqu Liu, Jian Zhang, Peng Luo
Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef
Maximizing Small Biopsy Patient Samples: Unified RNA-Seq Platform Assessment of over 120,000 Patient Biopsies
P. Sean Walsh, Yangyang Hao, Jie Ding, Jianghan Qu, Jonathan Wilde, Ruochen Jiang, Richard T. Kloos, Jing Huang, Giulia C. Kennedy
Journal of Personalized Medicine.2022; 13(1): 24. CrossRef

7,954 View
226 Download
7 Web of Science
7 Crossref

Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro: Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim; Cancer Res Treat. 2019;51(2):696-705. Published online August 13, 2018; DOI: https://doi.org/10.4143/crt.2018.249

Abstract PDF PubReader ePub

Purpose
Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect.
Materials and Methods
Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively.
Results
DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells.
Conclusion
Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Citations

Citations to this article as recorded by

The role of KDM4A‐mediated histone methylation on temozolomide resistance in glioma cells through the HUWE1/ROCK2 axis
Xi‐Xi Li, Jia‐Kun Xu, Wei‐Jie Su, Hong‐Lin Wu, Kun Zhao, Chang‐Ming Zhang, Xiang‐Kun Chen, Li‐Xuan Yang
The Kaohsiung Journal of Medical Sciences.2024; 40(2): 161. CrossRef
Glioblastoma Therapy: Past, Present and Future
Elena Obrador, Paz Moreno-Murciano, María Oriol-Caballo, Rafael López-Blanch, Begoña Pineda, Julia Gutiérrez-Arroyo, Alba Loras, Luis Gonzalez-Bonet, Conrado Martinez-Cadenas, José Estrela, María Marqués-Torrejón
International Journal of Molecular Sciences.2024; 25(5): 2529. CrossRef
Exploring Disulfiram’s Anticancer Potential: PLGA Nano-Carriers for Prolonged Drug Delivery and Potential Improved Therapeutic Efficacy
Ibrahim Dumbuya, Ana Maria Pereira, Ibrahim Tolaymat, Adnan Al Dalaty, Basel Arafat, Matt Webster, Barbara Pierscionek, Mouhamad Khoder, Mohammad Najlah
Nanomaterials.2024; 14(13): 1133. CrossRef
Targeting Retinaldehyde Dehydrogenases to Enhance Temozolomide Therapy in Glioblastoma
Rafael Jiménez, Andrada Constantinescu, Muhube Yazir, Paula Alfonso-Triguero, Raquel Pequerul, Xavier Parés, Mileidys Pérez-Alea, Ana Paula Candiota, Jaume Farrés, Julia Lorenzo
International Journal of Molecular Sciences.2024; 25(21): 11512. CrossRef
Clinical, pharmacological, and formulation evaluation of disulfiram in the treatment of glioblastoma - a systematic literature review
Beáta-Mária Benkő, Dimitrios A. Lamprou, Anna Sebestyén, Romána Zelkó, István Sebe
Expert Opinion on Drug Delivery.2023; 20(4): 541. CrossRef
Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma
Katja Werlenius, Sara Kinhult, Tora Skeidsvoll Solheim, Henriette Magelssen, David Löfgren, Munila Mudaisi, Sofia Hylin, Jiri Bartek, Michael Strandéus, Magnus Lindskog, Havyan Bahroz Rashid, Louise Carstam, Sasha Gulati, Ole Solheim, Jiri Bartek, Øyvind
JAMA Network Open.2023; 6(3): e234149. CrossRef
Drug repositioning of disulfiram induces endometrioid epithelial ovarian cancer cell death via the both apoptosis and cuproptosis pathways
YAPING GAN, TING LIU, WEIFENG FENG, LIANG WANG, LI LI, YINGXIA NING
Oncology Research.2023; 31(3): 333. CrossRef
Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways
Yao Liu, Xin Guan, Meiling Wang, Naixue Wang, Yutong Chen, Baolei Li, Zhuxuan Xu, Fangwei Fu, Cheng Du, Zhendong Zheng
Bioengineered.2022; 13(3): 6579. CrossRef
Disulfiram in glioma: Literature review of drug repurposing
Shiyu Zhong, Shengyu Liu, Xin Shi, Xudong Zhang, Kunhang Li, Guojun Liu, Lishuai Li, Shanwei Tao, Bowen Zheng, Weichen Sheng, Ziyin Ye, Qichen Xing, Qingqing Zhai, Lijie Ren, Ying Wu, Yijun Bao
Frontiers in Pharmacology.2022;[Epub] CrossRef
Multimodal targeting of glioma with functionalized nanoparticles
Hany E. Marei
Cancer Cell International.2022;[Epub] CrossRef
Formulation Comprising Arsenic Trioxide and Dimercaprol Enhances Radiosensitivity of Pancreatic Cancer Xenografts
Renyan Tang, Jianmin Zhu, Ying Liu, Ning Wu, Jinbin Han
Technology in Cancer Research & Treatment.2021;[Epub] CrossRef
Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
Hyeon Ji Kim, Tae-Jun Kim, Yu Gyung Kim, Chaeeun Seong, Jin-Hwa Cho, Wanil Kim, Kyung-Ha Lee, Do-Yeon Kim
Pharmaceutics.2021; 13(9): 1410. CrossRef
Disulfiram Sensitizes a Therapeutic-Resistant Glioblastoma to the TGF-β Receptor Inhibitor
Chan-Chuan Liu, Cheng-Lin Wu, Meng-Xuan Lin, Chun-I Sze, Po-Wu Gean
International Journal of Molecular Sciences.2021; 22(19): 10496. CrossRef
Repurposing Disulfiram for Targeting of Glioblastoma Stem Cells: An In Vitro Study
Lisa Zirjacks, Nicolai Stransky, Lukas Klumpp, Lukas Prause, Franziska Eckert, Daniel Zips, Sabine Schleicher, Rupert Handgretinger, Stephan M. Huber, Katrin Ganser
Biomolecules.2021; 11(11): 1561. CrossRef
The combination of disulfiram and copper for cancer treatment
Hong Li, Jingyu Wang, Chunfu Wu, Lihui Wang, Zhe-Sheng Chen, Wei Cui
Drug Discovery Today.2020; 25(6): 1099. CrossRef
Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme
Jinyeong Choi, Gaeun Kim, Su Bin Cho, Hyung-Jun Im
Journal of Nanobiotechnology.2020;[Epub] CrossRef
Disulfiram as a Therapeutic Agent for Metastatic Malignant Melanoma—Old Myth or New Logos?
Francisco Meraz-Torres, Sarah Plöger, Claus Garbe, Heike Niessner, Tobias Sinnberg
Cancers.2020; 12(12): 3538. CrossRef
Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents
Elmira Ekinci, Sagar Rohondia, Raheel Khan, Qingping P. Dou
Recent Patents on Anti-Cancer Drug Discovery.2019; 14(2): 113. CrossRef

9,675 View
297 Download
20 Web of Science
18 Crossref

First
Prev
Page of 1
Next
Last

Search