Abstract
Metastatic melanoma is a tumour exhibiting high resistance to most ways of treatment. Advances in our knowledge of immune reactions between the tumour and its host as well as the advances in molecular biology paved the way for the development of new and more effective treatment methods.
Immunotherapy of metastatic melanoma targets particularly CTLA-4 a PD-1 receptors, the blockade of which enhances the activity of cytotoxic T-lymphocytes and antitumour immunity. The most effective CTLA-4 inhibitor ipilimumab received approval in the setting of metastatic melanoma therapy from both the FDA and EMA, based on the results of the CA 184-002 trial.
The drug is the first agent that succeeded in significantly extending overall survival of patients. Treatment response rates are only 20-30%, but are long-term.
One of the most important signal pathways for melanoma is the MAPK/ERK cascade activated by BRAF mutation. Vemurafenib, a selective inhibitor of V600E mutated BRAF kinase, is capable to produce high rates of treatment response in patients with metastatic melanoma.
These responses occur quite early, in the first days to weeks after treatment initiation, and their rate exceeds 50%. Promising results of clinical studies are currently emerging evaluating new BRAF and MEK inhibitors such as dabrafenib or trametinib.
Other objectives envisaged in the treatment of metastatic melanoma is the identification of factors predictive of treatment response to ipilimumab, and interventions attempting to delay or prevent the formation of resistance to BRAF inhibitors.