Correlation of circulating tumor DNA with targeted therapy and drug resistance mechanism of metastatic colorectal cancer
LI Jian-ying1, MAO Yu-huan1, ZHANG Xiao2, ZHOU Qiong2, TAN Li-ming2
1.The First Hospital of Changsha City, Changsha, Hunan 410005, China; 2. The People's Hospital of Hunan Province (The First Hospital Affiliated to Hunan Normal University), Changsha, Hunan 410001, China
Abstract：Objective To explore the possible mutations associated with drug resistance in metastatic colorectal cancer (mCRC), to verify whether circulating tumor DNA (ctDNA) can be used as a molecular marker of mutations associated with mCRC detection and drug resistance as well as the possible drug resistance mechanisms of mCRC. Methods Through the dynamic monitoring of KRAS, BRAF and PIK3CA gene point mutations in ctDNA in multi-stages in mCRC patients with continuous anti-epidermal growth factor receptor (EGFR) therapy, the changes in tumor gene mutation spectrum under drug treatment were constructed and drug-resistance-related point mutations were screened. The multiplexed cell lines were selected according to the point mutation, and multidrug resistance of multiple groups of cell lines was analyzed by MTS assay. The drug pressure was analyzed by real-time quantitative PCR (RT-qPCR). Results KRAS (G12D), PIK3CA (H1047R) and BRAF (V600E) mutations related to drug resistance of mCRC were screened by clinical data analysis, and enrolled in the follow-up study. NCI-H747, SW948 and SW1417 cell lines were selected as KRAS (G12D), PIK3CA (H1047R) and BRAF (V600E) point mutation cell lines, respectively, and the wild-type cell line of C2BBe1 was used as the background. IC50 was performed by MTS experiments. It was found that the wild-type cells were significantly higher than mutation cells for the incidence of cetuximab and panitumumab. The cells were diluted by basal cells. After 3-day cultivation, the relative levels of the mutant genes were higher in the cetuximab group and the panitumumab group than in the non-drug group as well as higher in the non-drug group than in the baseline group. Conclusion Drug-resistance-related point mutations can be determined by ctDNA detection. The growth rate of metastatic colorectal cancer cells can be increased by KRAS (G12D), PIK3CA (H1047R) and BRAF (V600E) mutations, and they are associated with the drug resistance of cetuximab and panitumumab.
李建英, 毛玉环, 张晓, 周琼, 谭黎明. 循环肿瘤DNA与转移性结直肠癌靶向治疗及耐药机制的相关研究[J]. 实用预防医学, 2021, 28(12): 1450-1454.
LI Jian-ying, MAO Yu-huan, ZHANG Xiao, ZHOU Qiong, TAN Li-ming. Correlation of circulating tumor DNA with targeted therapy and drug resistance mechanism of metastatic colorectal cancer. , 2021, 28(12): 1450-1454.
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2021, Vol. 28 
