Copper suppression as cancer therapy: the rationale for copper chelating agents in BRAFV600 mutated melanoma.

The successful targeting of oncogenic BRAFV600 represents one of the landmark breakthroughs in therapy for advanced melanoma. While the initial clinical benefit can be dramatic, resistance is common due to a number of mechanisms, including MAPK pathway reactivation. Recent data have revealed a novel role for copper (Cu) in BRAF signaling with potential clinical implications. The history, preclinical data and efficacy of Cu chelating agents in cancer, specifically tetrathiomolybdate, will be reviewed with a focus on the rationale for targeting the MAPK cascade in melanoma through novel combination strategies.