Cyclin-dependent kinases as therapeutic targets in melanoma

Decades of scientific insights have led to a recent expansion of the therapeutic menu for melanoma. Despite these advances, the current targeted therapies and immune checkpoint agents continue to yield suboptimal response and cure rates. Hitherto, the most effective targeted therapy strategies have centered on effectors in the mitogen-activated protein kinase (MAPK) pathway. This review focuses on the emerging evidence of combinatorial approaches targeting both MAPK signaling and dysregulations in cell-cycle checkpoints. We discuss the prospects and limitations of utilizing strategies that promote cellular senescence, such as inhibition of the interphase cyclin-dependent kinases (CDKs) and highlight the current state of CDK drug discovery in melanoma.