Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Molecular Evolutionary Process of Advanced Gastric Cancer During Sequential Chemotherapy Detected by Circulating Tumor DNA
29 Pages Posted: 24 Sep 2021
More...Abstract
Purpose: Chemotherapy is the major strategy for advanced gastric cancer (AGC) patients, where its efficacy has largely plateaued. Tumor evolutionary theory provides a promising strategy to optimize paradigm of cancer treatment, while current data of molecular changes during sequential chemotherapy is too insufficient to understand evolutionary process in tumors.
Methods: Here, we performed NGS analysis on 100 circulating tumor DNA (ctDNA) samples collected from 27 AGC patients during treatment of sequential chemotherapy. We observed dynamic changes of copy number instability (CNI) and gene-level copy number variations (CNVs) during the treatment.
Results: Gene-level CNV profiles were similar between baseline and end of treatment. Subsequent regimens did not significantly change the CNV profiles driven by first-line regimens. Based on changes of copy number values of genes during treatment, resistance related genes of all four regimens were identified, respectively. These genes could be enriched into several common oncologic pathways, while exhibited a high inter-patient heterogeneity. Genes with different copy number values between baseline and end of treatment could be the targets of by molecular matched therapy.
Conclusions: Our study provides important information to understand molecular evolutionary process of AGS patients during sequential chemotherapy first and can help to optimize future treatment strategies.
Funding: The study was supported by National Science Foundation of China (81972707 and 81802319) and Collaborative innovation cluster project of Shanghai Municipal Health Commission (2020CXJQ03).
Declaration of Interest: None to declare.
Ethical Approval: The protocol was approved by ethics committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China.
Keywords: gastric cancer, sequential chemotherapy, dynamic ctDNA analysis, copy number variations, tumor evolution
Suggested Citation: Suggested Citation