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 ...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 allelespecific inhibitors against KRASG12C.Targeting the remaining RAS mutants would require further experimental elucidation ofRAS signal transduction,RASaltered 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.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:82072360,82102704,82072624,81872481Natural Science Foundation of Zhejiang Province,Grant/Award Number:LBY20H160002。
文摘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 allelespecific inhibitors against KRASG12C.Targeting the remaining RAS mutants would require further experimental elucidation ofRAS signal transduction,RASaltered 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.
