Drug tolerance to target therapy in melanoma revealed at single cell level: What next?

Abstract Drug resistance strongly impairs the efficacy of virtually every kind of anticancer therapy. This phenomenon is commonly fueled by intrinsic or acquired mechanisms. In this mini-review, focusing on BRAF-mutated melanoma as prototypical example, we analyze how recent studies that make use of single cell analysis identify the involvement of distinct transcriptional trajectories as the common thread at the basis of drug tolerance. The identification of these transcriptional trajectories provide a mechanistic basis for the development of both intrinsic and acquired drug resistance. These studies also suggest that hitting these transcriptional trajectories through personalized adaptive treatments can delay or abrogate the onset of drug resistance.