CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer.

@article{Johnson2016CDK12IR,
  title={CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer.},
  author={Shawn F. Johnson and Cristina Cruz and Ann Katrin Greifenberg and Sofia Dust and Daniel G Stover and David P Chi and Benjamin Primack and Shiliang A Cao and Andrea J. Bernhardy and Rhiannon S Coulson and J S L{\'a}zaro and Bose S. Kochupurakkal and Heather H. Sun and Christine L Unitt and Lisa A. Moreau and Kristopher Sarosiek and Maurizio Scaltriti and Dejan Juric and Jos{\'e} Baselga and Andrea L. Richardson and Scott J Rodig and Alan D' Andrea and Judith Balma{\~n}{\`a} and Neil W. Johnson and Matthias Geyer and Violeta Serra and Elgene Lim and Geoffrey I. Shapiro},
  journal={Cell reports},
  year={2016},
  volume={17 9},
  pages={2367-2381}
}
Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of HR. In BRCA-mutated triple-negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs), dinaciclib ablates restored HR… CONTINUE READING
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