Author:
Zhu Chunxiao,Guan Xiaoqing,Zhang Xinuo,Luan Xin,Song Zhengbo,Cheng Xiangdong,Zhang Weidong,Qin Jiang-Jiang
Abstract
AbstractKirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with drugs is challenging because KRAS is considered undruggable due to the lack of classic drug binding sites. Over the past 40 years, great efforts have been made to explore routes for indirect targeting of KRAS mutant cancers, including KRAS expression, processing, upstream regulators, or downstream effectors. With the advent of KRAS (G12C) inhibitors, KRAS mutations are now druggable. Despite such inhibitors showing remarkable clinical responses, resistance to monotherapy of KRAS inhibitors is eventually developed. Significant progress has been made in understanding the mechanisms of drug resistance to KRAS-mutant inhibitors. Here we review the most recent advances in therapeutic approaches and resistance mechanisms targeting KRAS mutations and discuss opportunities for combination therapy.
Funder
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province
National Key Research and Development Program of China
Shanghai Frontiers Science Center of TCM Chemical Biology, and Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine
Medical Science and Technology Project of Zhejiang Province
Program of Zhejiang Provincial TCM Sci-tech Plan
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Medicine
Cited by
48 articles.
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