Genetic Drivers of Sensitivity or Resistance to RAS(ON) Multiselective Inhibitors in NRAS-Mutated Melanoma.
- Open access
RMC-7977 and daraxonrasib show potent activity against NRAS-mutated melanoma but face resistance mechanisms involving Ppia and Map2k1 mutations.
- Why it matters: Understanding resistance pathways is crucial because NRAS-mutated melanoma lacks effective pathway-targeted therapies after immunotherapy failure, limiting treatment options.
- What they did: The study tested RAS(ON) inhibitors in preclinical models and analyzed clinical cases, identifying mutations in Ppia and Map2k1 associated with resistance to monotherapy.
- The result: Findings suggest daraxonrasib has therapeutic potential for NRAS-mutated melanoma, but resistance mechanisms highlight the need for combination treatments to enhance efficacy.