Jacqueline Maphutha, Danielle Twilley, Mona Dawood, Thomas Efferth, Namrita Lall
Metastatic melanoma is the most lethal form of skin cancer, accounting for most skin cancer-related deaths. Immunotherapies and targeted therapies have improved overall and progression-free survival rates in metastatic melanoma patients. The effectiveness of these therapies decreases due to multidrug resistance (MDR). In contrast to previous reviews, this review extensively highlights the hallmarks of MDR and strategies for reversal of MDR. The review also critically evaluates the challenges in clinical translation of phytochemicals for metastatic melanoma and strategies to overcome these challenges. This review also highlights the various gaps that exist in metastatic melanoma (e.g., vascularized organ-on-a-chip model has not been developed for melanoma which is largely influenced by angiogenesis). These gaps offer novel avenues that could be explored for clinical translation of phytochemicals.