Open AccessTargeting RAS mutants in malignancies: successes, failures, and reasons for hope
Author(s) -
Yang Hang,
Zhou Xinyi,
Fu Dongliang,
Le Chenqin,
Wang Jiafeng,
Zhou Quan,
Liu Xiangrui,
Yuan Ying,
Ding Kefeng,
Xiao Qian
Publication year - 2023
Publication title -
cancer communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.119
H-Index - 53
ISSN - 2523-3548
DOI - 10.1002/cac2.12377
Subject(s) - hras , neuroblastoma ras viral oncogene homolog , kras , cancer research , biology , mutant , mutation , gene , computational biology , medicine , genetics
RAS genes are the most frequently mutated oncogenes and play critical roles in the development and progression of malignancies. The mutation, isoform ( KRAS , HRAS , and NRAS ), position, and type of substitution vary depending on the tissue types. Despite decades of developing RAS‐targeted therapies, only small subsets of these inhibitors are clinically effective, such as the allele‐specific inhibitors against KRAS G12C . Targeting the remaining RAS mutants would require further experimental elucidation of RAS signal transduction, RAS‐altered metabolism, and the associated immune microenvironment. This study reviews the mechanisms and efficacy of novel targeted therapies for different RAS mutants, including KRAS allele‐specific inhibitors, combination therapies, immunotherapies, and metabolism‐associated therapies.