Review of genetics of melanoma including analysis of the mutational signatures of melanoma tumors continues to cement the causative role of UV exposure in melanoma pathogenesis. Melanomas from sun-exposed skin areas have distinct mutational signatures including C to T transitions indicative of UV-induced damage. It is thus necessary to continue spreading awareness on how to decrease the risk factors of developing the disease while at the same time working for a cure.
- phase III
Review of the available data to best guide initial treatment choice and the sequence of treatments for patients with BRAF Val600 mutant melanoma.
Phase III trial of treatment-naive metastatic melanoma comparing tremelimumab with physician’s choice standard-of-care chemotherapy failed to show an improved overall survival for the immunotherapy antibody.
Study finds phosphorylation of Mps1 by BRAFV600E prevents Mps1 degradation and contributes to chromosome instability in melanoma. The results raise the possibility that targeting the oncogenic BRAF and S281-phosphorylated Mps1, especially when used in combination could potentially provide great therapeutic opportunities for cancer treatment.
Two University of Colorado Cancer Center studies show that silibinin protects against UVB damage and kills cells damaged by UVA — but is not at all toxic in healthy cells. Sibinin is a milk thistle extract now shown to kill skin cells mutated by UVA radiation and protects against damage by UVB radiation, potentially protecting against UV-induced skin cancer and photo-aging.
The European Medicines Agency has granted an accelerated review process for GSK’s trametinib, a MEK inhibitor, for treatment of metastatic melanoma. GSK has filedresults from the monotherapy phase III METRIC trial as well as phase I/II trial results of the combination of trametinib plus dabrafenib, a BRAF inhibitor. Phase III combination trials of trametinib plus dabrafenib both versus the current approved BRAF inhibitor, vemurafenib, and against dabrafenib alone are in progress.
Results of the phase III SYMMETRY trial in stage IV metastatic melanoma patients don’t show an improvement in PFS when elesclomol was added to paclitaxel chemotherapy. But, patients with normal LDH levels did have a statistically significant improvement in median PFS for the combination therapy.