Recent advancement in targeting the KRAS-G12C mutant for cancer therapy
10.16438/j.0513-4870.2020-1485
- VernacularTitle:特异靶向KRAS-G12C突变的抗肿瘤药物研究进展
- Author:
Xin LI
1
;
Yi-jun WANG
2
;
Ping-yu LIU
2
Author Information
1. School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
2. Pharmacy Department, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China
- Publication Type:Research Article
- Keywords:
KRAS mutated cancer;
KRAS-G12C mutant;
anticancer drug;
covalent inhibitor;
proteolysis-targeting chimeras;
combination therapy
- From:
Acta Pharmaceutica Sinica
2021;56(2):374-382
- CountryChina
- Language:Chinese
-
Abstract:
RAS, as a well-known proto-oncogene, is the most frequently mutated oncogene in human cancers, yet tremendous efforts over the past 30 years have failed to develop effective therapies for RAS-mutant cancer. Recently, specifically targeting the KRAS-G12C mutant, a frequently occurring KRAS mutation in human cancers, has shown promise in conquering KRAS-mutant cancers, and has inspired interest in this direction. We herein review the very recent progress achieved in the development of covalent inhibitors towards KRAS-G12C mutant, in combinational therapies and in proteolysis-targeting chimeras (PROTACs)-based approaches to disrupt KRAS-G12C protein. We provide insights for drug discovery against KRAS-G12C-mutated tumors and discuss the potential challenges in this field.
