文献类型：期刊文献

英文题名：Targeted therapy for KRAS G12C-mutated colorectal cancer: advances, challenges, and future directions

作者：Lin, Yang[1];Cheng, Shuai-Hua[1];Wang, Di[1];Zhang, Sheng-Hui[1];Li, Hong-Ling[2]

第一作者：Lin, Yang

通信作者：Li, HL[1]

机构：[1]Gansu Univ Tradit Chinese Med, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Peoples Hosp, Dept Oncol, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Peoples Hosp, Dept Oncol, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2025

卷号：15

期号：12

起止页码：5084

外文期刊名：AMERICAN JOURNAL OF CANCER RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001656707000003)】；

基金：This work was supported by the joint fund project of Gansu Provincial Department of Science and Technology (23JRRA1545) .

语种：英文

外文关键词：Colorectal cancer; KRAS G12C mutation; combination therapy

摘要：Colorectal cancer (CRC) is among the most prevalent malignancies worldwide, with approximately 40% of the patients carrying KRAS mutations. Among these, the KRAS G12C mutation accounts for approximately 4% of the cases. This mutation introduces a unique cysteine residue at codon 12, enablingcovalent bindingand rendering KRAS G12C a tractable therapeutic target. Recently, selective small-molecule inhibitors of KRAS G12C, including sotorasib and adagrasib, have shown encouraging activity in early clinical trials, indicating potential clinical benefits for this subset of patients. However, their translation into routine clinical practice has been challenged by intrinsic and acquired resistance, treatment-related toxicities, and the absence of reliable predictive biomarkers. The aim of this study is to construct a clear knowledge framework that could inform the design of future clinical trials and optimize clinical practice. Future studies should focus on developing more potent next-generation inhibitors, exploring and optimizing rational combination strategies with other targeted agents or immunotherapies, investigating innovative therapeutic methods, and systematically identifying and validating predictive biomarkers. Collectively, with these efforts, we aim to enhance the efficacy, overcome resistance, and advance precision therapyfor patients with KRAS G12C-mutant CRC.