New drug targets in metastatic melanoma

• Published in: The Journal of pathology Vol. 232; no. 2; pp. 134 - 141
• Main Authors: Homet, Blanca, Ribas, Antoni
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2014; Wiley Subscription Services, Inc
• Subjects: Animals; Antineoplastic Agents - therapeutic use; BRAF mutant; Drug Discovery; Drug Resistance, Neoplasm; Genetic Predisposition to Disease; Humans; immunotherapy; Immunotherapy - methods; Melanoma - drug therapy; Melanoma - genetics; Melanoma - immunology; Melanoma - metabolism; Melanoma - secondary; metastatic melanoma; Molecular Targeted Therapy; Phenotype; Protein Kinase Inhibitors - therapeutic use; Signal Transduction - drug effects; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; metastatic melanoma; immunotherapy; BRAF mutant
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.4259

Over the past 30 years, and despite extensive clinical research, the treatment options for metastatic melanoma have been limited. Single‐agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimes have failed to show significant improvement in overall survival. Recent advances and in‐depth understanding of the biology of melanoma have contributed in the development of new agents and to a change in the consideration of melanoma as one of the most therapy‐resistant malignancies. Since the discovery of activating mutations in the BRAF oncogene, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma, with unprecedentedly high response rates. Inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided clinically validated targets for cancer immunotherapy, resulting in durable tumour responses. The combination of both approaches may result in additional benefits. Here we discuss current molecular targeted treatment options, immunotherapy and promising ongoing research to develop new strategies to treat melanoma. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.