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

doi:10.1016/j.celrep.2016.10.077

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Article

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

Cell reports - 22 Nov 2016

Johnson Shawn F, Cruz Cristina, Greifenberg Ann Katrin, Dust Sofia, Stover Daniel G, Chi David, Primack Benjamin, Cao Shiliang, Bernhardy Andrea J, Coulson Rhiannon, Lazaro Jean-Bernard, Kochupurakkal Bose, Sun Heather, Unitt Christine, Moreau Lisa A, Sarosiek Kristopher A, Scaltriti Maurizio, Juric Dejan, Baselga José, Richardson Andrea L, Rodig Scott J, D'Andrea Alan D, Balmaña Judith, Johnson Neil, Geyer Matthias, Serra Violeta, Lim Elgene, Shapiro Geoffrey I

Abstract excerpt

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...

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Identifiers

PMID: 27880910
DOI: 10.1016/j.celrep.2016.10.077
PMCID: PMC5176643

Genes

CDK12
BRCA1

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 6 Sept 2026. Manifest publication-graph-cohort-2026-09-06.1.

Source receipt: pubmed, retrieved 6 Sept 2026.

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