UCLA

Key PointsClinical therapeutics for advanced-stage melanoma have improved dramatically with the development of BRAF and MEK inhibitors, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell-death protein 1 (PD-1) blocking antibodies, and a modified oncolytic herpes virus that is delivered intratumourallyThe overall survival of patients with advanced-stage melanoma has improved from ∼9 months before 2011 to an as yet undefined timeframe, with a subset of patients having ongoing long-term tumour controlMelanoma, particularly cutaneous melanoma, is amendable to immunotherapy for various reasons, including extensive tumour infiltration by T cells, a high mutational load, and crosstalk between oncogenic signalling pathways and immunobiologyResistance mechanisms to BRAF-targeted treatments and immunotherapies are being elucidated; reactivation of the MAPK pathway is common after BRAF inhibition, whereas the effectiveness of both approaches might be limited by loss of tumour antigen presentation and T-cell traffickingTo move the field of clinical therapeutics forward, a greater focus on specific patient populations (based on serum lactose dehydrogenase levels, ECOG performance status, and number of metastases), as well as on landmark progression-free and overall survival measures, will be required in clinical trials