Sensitizing Lung Cancer to Immunotherapy with a RAS(ON) Inhibitor Doublet

First-generation RAS inhibitory drugs have failed to live up to expectations in the clinic, but a preclinical study of a combination of two ON-state RAS inhibitors, one mutant-selective and one targeting all RAS forms, shows greatly reduced development of drug resistance. Most strikingly, this RAS inhibitor doublet combines very effectively with immune checkpoint blockade, leading to complete immune elimination of even highly refractory cancers with immune-cold tumor microenvironments, generating hope for real progress in tackling RAS-mutant tumors in the clinic. See related article by Wei et al., p. 1152.