The Therapeutic Potential of Metformin for Melanoma

ARBE, MARÍA FLORENCIA; PORTILLO, FRANCO A; GLIKIN, GERARDO CLAUDIO; FINOCCHIARO, LILIANA M. E; VILLAVERDE MARCELA SOLANGE. S.

Horizons in Cancer Research

NOVA Science

Año: 2020;

Melanoma is the most aggressive form of human skin cancer and its malignant progression demands changes in metabolic pathways. In addition, the melanoma most prevalent oncogenic mutation BRAF (50%), has been particularly related with glucose metabolism. Metformin is a widely used antidiabetic drug, safe and very well tolerated. Since metformin inhibits mitochondrial complex I, ATP/ADP ratio decreases and actives AMPK, which in turn inhibits mammalian target of rapamycin (mTOR). At present, more than 300 clinical trials are being conducted to investigate the role of metformin in prevention and treatment of different types of cancers, including melanoma. Here, we will discuss the cytotoxic effects and the mechanism displayed by metformin, alone or in combination with other agents. A better understanding of metformin-induced metabolic changes could aim to discover new drugs, enhancing the efficacy of current melanoma therapeutics.