Genetic Drivers of Sensitivity or Resistance to RAS(ON) Multi-Selective Inhibitors in NRAS-Mutated Melanoma - PubMed
4 hours ago
- #NRAS melanoma
- #RAS inhibitors
- #Drug resistance
- RAS(ON) multi-selective inhibitors like RMC-7977 and daraxonrasib show potent anti-proliferative activity against NRAS-mutated melanoma.
- Resistance to RMC-7977 monotherapy in preclinical models arises via mutations in Ppia (CYPA) or Map2k1 (MEK1).
- Daraxonrasib demonstrated anti-tumor activity in one NRAS-mutated melanoma patient, but progressive disease in another with co-occurring NRAS and MAP2K1 mutations.
- The findings support daraxonrasib's potential for treating NRAS-mutated melanoma and highlight monotherapy resistance mechanisms.
- Combination therapies may be needed to improve outcomes for patients with NRAS-mutated melanoma.