Copper suppression as cancer therapy: the rationale for copper chelating agents in BRAF^V600 mutated melanoma

The successful targeting of oncogenic BRAF^V600 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.