Molecular Targeted Therapy in Melanoma: A Way to Reverse Resistance to Conventional Drugs

Francesca      Maira; Alessia      Catania; Saverio      Candido; Alessia      Erika Russo; James      A. McCubrey; Massimo      Libra; Grazia      Malaponte; Concettina      Fenga

Abstract

Cutaneous melanoma is the most aggressive skin cancer. Beside surgery, it is treated with chemotherapy and immunotherapy. However, many patients relapse after adjuvant therapy. The recent identification of several key molecular pathways implicated in the pathogenesis of melanoma is spreading development of a number of new translational targeted therapies which could play an important role in overcoming or minimizing resistance to chemotherapeutic drugs and proapoptotic therapies. This review summarizes environmental factors and the most significant molecular events involved in melanoma pathogenesis, disclosing mechanisms responsible for drug resistance and pointing out the clinical view for emerging targeted therapies. Standard therapies and an update on the current clinical trials are also described.

Keywords: Drug resistance, melanoma, BRAF, PI3K/AKT/mTOR, AF/MEK/ERK, sensitivity, targeted therapy, MEK, ERK, gene mutations