Circulating Tumor DNA Is Capable of Monitoring the Therapeutic Response and Resistance in Advanced Colorectal Cancer Patients Undergoing Combined Target and Chemotherapy

Cao, Hua1; Liu, Xinyi2; Chen, Yixin1; Yang, Pan2; Huang, Tanxiao2; Song, Lele2; Xu, Ruilian1

2020-04-07

10.3389/fonc.2020.00466

Frontiers in Oncology   影响因子和分区

2234-943X

Colorectal cancer (CRC) is a highly lethal disease worldwide. The majority of patients receiving targeted therapy or chemotherapy develop drug resistance, while its molecular mechanism remains to be elucidated. The plasma circulating tumor DNA (ctDNA) exhibited the potential in identifying gene variations and monitoring drug resistance in CRC treatment. In this study, we monitored the ctDNA mutational changes in advanced CRC patients underwent first-line therapy with bevacizumab and cetuximab combined with chemotherapy. The mutation spectrum of 43 patients was established by a 605-gene next-generation sequencing (NGS) panel. The baseline measurement shows that genes with the highest mutation frequency were TP53 (74%), APC (58%), KRAS (40%), SYNE1 (33%), LRP1B (23%), TOP1 (23%), and PIK3CA (21%). Mutations in TP53, APC, and KRAS were detected in 29 paired plasma and tissue samples with the consistency of 81, 67, and 42%, respectively. Clinically targetable gene mutations, such as APC, RNF43, SMAD4, BRAD1, KRAS, RAF1, and TP53, were also identified in ctDNA. The overall consistency between ctDNA and tissue samples was 54.6%. Alleviation of mutational burden in BRAF, KRAS, AMER1, and other major driving genes was observed following the first-line therapy. Patients with KRAS and TP53 mutations in tissues appeared to benefit more than the wild-type counterpart. The dynamic change of plasma mutation status was consistent with the tissue tumor burden and was closely correlated with disease progression. In conclusion, ctDNA monitoring is a useful method for molecular genotyping of colorectal cancer patients. Dynamic changes in resistance can be sensitively monitored by gene variation status, which potentially helps to develop treatment strategy.

colorectal cancer ctDNA NGS sequencing bevacizumab cetuximab monitoring resistance

SCI

英语

第一 ; 通讯

Sanming project of Shenzhen People's Hospital[SYLY201725]

Oncology

Oncology

WOS:000529000100001

FRONTIERS MEDIA SA

Web of Science

1.Southern Univ Sci & Technol, Dept Oncol, Shenzhen Peoples Hosp, Sch Clin Med 2,Jinan Univ,Affiliated Hosp 1, Shenzhen, Peoples R China
2.HaploX Biotechnol Co Ltd, Shenzhen, Peoples R China

Cao, Hua,Liu, Xinyi,Chen, Yixin,et al. Circulating Tumor DNA Is Capable of Monitoring the Therapeutic Response and Resistance in Advanced Colorectal Cancer Patients Undergoing Combined Target and Chemotherapy[J]. Frontiers in Oncology,2020,10.

Cao, Hua.,Liu, Xinyi.,Chen, Yixin.,Yang, Pan.,Huang, Tanxiao.,...&Xu, Ruilian.(2020).Circulating Tumor DNA Is Capable of Monitoring the Therapeutic Response and Resistance in Advanced Colorectal Cancer Patients Undergoing Combined Target and Chemotherapy.Frontiers in Oncology,10.

Cao, Hua,et al."Circulating Tumor DNA Is Capable of Monitoring the Therapeutic Response and Resistance in Advanced Colorectal Cancer Patients Undergoing Combined Target and Chemotherapy".Frontiers in Oncology 10(2020).