Abstract
Melanoma is a highly aggressive tumor and almost always fatal when metastatic. Herein, we discuss recent findings on the mechanisms of resistance of human cutaneous melanoma. To achieve a precision medicine approach, the heterogeneity and plasticity of tumor cells are two crucial aspects to be investigated in depth. In fact, to understand the mechanisms that cells use to acquire a resistant phenotype after chemotherapy or how resistant cells inside the tumor are selected, it is the most important issue for a successful therapy. Since new therapeutic strategies are trying to go in this direction, we discuss here the state of the art of the research and the clinical impact of these strategies. We also discuss and suggest future research directions to develop approaches able to define the best concentration and time of exposure of the drug or the cocktails of drugs for each specific patient based on his/her biological features.