Nature Communications (Oct 2022)

CDK12 is hyperactivated and a synthetic-lethal target in BRAF-mutated melanoma

  • Thibault Houles,
  • Geneviève Lavoie,
  • Sami Nourreddine,
  • Winnie Cheung,
  • Éric Vaillancourt-Jean,
  • Célia M. Guérin,
  • Mathieu Bouttier,
  • Benoit Grondin,
  • Sichun Lin,
  • Marc K. Saba-El-Leil,
  • Stephane Angers,
  • Sylvain Meloche,
  • Philippe P. Roux

DOI
https://doi.org/10.1038/s41467-022-34179-8
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 16

Abstract

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In patients with melanoma, increased RAS/mitogen-activated protein kinase (MAPK) pathway activity is known to drive chemotherapy resistance. Here, the authors identify CDK12 as a downstream effector of the RAS/MAPK pathway and therapeutic target which mediates chemotherapy resistance through increased expression of DNA repair associated genes.