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No longer an untreatable disease: How targeted and immunotherapies have changed the management of melanoma patients

Maria Romina Girotti, Grazia Saturno, Paul Lorigan, Richard Marais

Review Article
Molecular Oncology, In Press, Uncorrected Proof, Available online 15 August 2014

Editor's comments:
This is a review which comprehensively covers the enormous progress made in recent years in the treatment of metastatic melanoma. Starting from the explanation of the biological mechanisms which underlie them, the authors clearly illustrate the basis in the development of the various target therapies, in particular BRAF and MEK inhibitors, and the different immunotherapeutic drugs, first of all the anti-CTLA-4 ipilimumab, followed by anti-PD-1 and anti-PD-L1, not forgetting to emphasize the importance of combination therapy, which are currently the main hope for further future progress.


The discovery that BRAF is a driver oncogene in cancer, and complementary improvements in our understanding of the immune system have resulted in new targeted and immune-therapies for metastatic melanoma. Targeted therapies achieve impressive clinical results in carefully selected patients but the development of resistance seems inevitable in most cases. Conversely, immune-checkpoints inhibitors can achieve long-term remission and cures, but in a smaller proportion of patients, and biomarkers to predict which patients will respond are not available. Nevertheless, melanoma has led the evolution of cancer treatment from relatively nonspecific cytotoxic agents to highly selective therapies and here we review the lessons from this paradigm shift in treatment and the opportunities for further improvements in outcomes for melanoma patients.