RAS(ON) Multiselective Inhibition Drives Antitumor Immunity in Preclinical Models of NRAS-Mutant Melanoma.

ABSTRACT: Targeted therapies for NRAS-mutant melanoma remain an unmet clinical need. In this study, we demonstrate that RMC-7977, a preclinical RAS(ON) multiselective inhibitor representative of the investigational agent daraxonrasib (RMC-6236), was able to elicit potent antitumor immune responses across multiple NRAS-mutant melanoma models. Treatment with RMC-7977 led to rapid tumor regressions driven by inhibition of MAPK signaling, upregulation of MHC and PD-L1 proteins, and enhanced infiltration of CD4+ and CD8+ T cells. Complete responses were dependent on adaptive immunity, as both CD4+ and CD8+ T cells were essential for extended survival. Resistance to treatment was marked by reduced T-cell infiltration, loss of MHC class I expression, and expansion of myeloid-derived suppressor cells. Combi

SUBMITTER: Anastacio Da Costa Carvalho L 

PROVIDER: S-EPMC12666865 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature