Topic: Drug Resistance in Melanoma: Mechanistic Insights and Overcoming Strategies

Melanoma, the most aggressive form of skin cancer originating from the transformation of melanocytes, continues to be a leading cause of death among cancer patients. The development and progression of this disease are linked to the accumulation of genetic alterations that account for the hyper-activation of cell survival pathways, with mutation of BRAF being the most frequent alteration. While surgery has traditionally been effective in treating early-stage disease, the landscape of metastatic melanoma treatment has undergone significant changes in recent years, thanks to the introduction of targeted therapies. This has resulted in a substantial decrease in patient mortality rates. The approval of BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib) for combination therapy has been fundamental for improving melanoma outcomes. However, the clinical benefit of these combination therapies is limited by the occurrence of drug resistance, which continues to drive the efforts of researchers in identifying new therapeutic targets. In this context, activating alternative signaling pathways to the MAP kinase pathway and disrupting metabolic pathways that confer a survival advantage may prove beneficial, in addition to employing immunotherapy-based strategies. By gaining a better understanding of the compensatory pathways activated by tumor cells in response to treatment with agents clinically available in melanoma, we anticipate further improvement in the cure of melanoma patients.

30 Sep 2024