CDK4/6 Inhibitors in Melanoma: A Comprehensive Review

Cells. 2021 May 28;10(6):1334. doi: 10.3390/cells10061334.

Abstract

Historically, metastatic melanoma was considered a highly lethal disease. However, recent advances in drug development have allowed a significative improvement in prognosis. In particular, BRAF/MEK inhibitors and anti-PD1 antibodies have completely revolutionized the management of this disease. Nonetheless, not all patients derive a benefit or a durable benefit from these therapies. To overtake this challenges, new clinically active compounds are being tested in the context of clinical trials. CDK4/6 inhibitors are drugs already available in clinical practice and preliminary evidence showed a promising activity also in melanoma. Herein we review the available literature to depict a comprehensive landscape about CDK4/6 inhibitors in melanoma. We present the molecular and genetic background that might justify the usage of these drugs, the preclinical evidence, the clinical available data, and the most promising ongoing clinical trials.

Keywords: Abemaciclib; CDK4; CDK4/6; CDK6; Palbociclib; Ribociclib; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Humans
  • Melanoma / drug therapy*
  • Molecular Targeted Therapy / methods
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6