Melanomas resistant to BRAF inhibitors show increased polyamine biosynthesis, driven by the activation of the oncogene c-Myc. This ultimately leads to increased mitochondrial activity and drug resistance. The study demonstrates that inhibiting polyamine biosynthesis can block this mechanism, overcoming drug resistance.

(Left) Synergistic cell death observed when combining BRAF inhibitors with polyamine biosynthesis inhibitors or mitochondrial activity inhibitors. (Right) Confirmation of synergistic anticancer effects when combining BRAF inhibitors and polyamine biosynthesis inhibitors.