145 (PB025) - Vertical inhibition of the MAPK pathway as potential treatment strategy in NRAS-mutant melanoma

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Background: Metastatic melanoma is the most aggressive form of skin cancer. Worldwide incidences of melanoma continue to rise, ranking melanoma as the sixth most common cancer. A large proportion of melanomas carry mutations in the mitogen-activated protein kinase (MAPK) signaling pathway leading to hyper-activation and proliferation. Driver mutations in BRAF V600(50%) and NRAS Q61(20%) are commonly found. FDA-approved kinase inhibitors that directly target BRAFV600E-mutated tumors have shown dramatic and long-lasting clinical efficacy, but relapses do occur.