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

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• 作者：Shawn F. Johnson¹ ; Cristina Cruz² ; ³ ; Ann Katrin Greifenberg⁴ ; ⁵ ; Sofia Dust⁴ ; ⁵ ; Daniel G. Stover¹ ; ⁶ ; ⁷ ; David Chi¹ ; Benjamin Primack⁸ ; ⁹ ; Shiliang Cao¹ ; Andrea J. Bernhardy¹⁰ ; Rhiannon Coulson¹¹ ; Jean-Bernard Lazaro⁸ ; Bose Kochupurakkal⁸ ; Heather Sun¹² ; Christine Unitt¹² ; Lisa A. Moreau⁸ ; ⁹ ; Kristopher A. Sarosiek¹ ; Maurizio Scaltriti¹³ ; Dejan Juric¹⁴ ; ¹⁵ ; José ; Baselga¹³ ; Andrea L. Richardson¹² ; ¹⁶ ; Scott J. Rodig¹² ; Alan D. D&rsquo ; Andrea⁸ ; ⁹ ; Judith Balmañ ; a³ ; Neil Johnson¹⁰ ; Matthias Geyer⁴ ; ⁵ ; Violeta Serra² ; Elgene Lim¹ ; ¹¹ ; ^{e.lim@garvan.org.au} ; Geoffrey I. Shapiro¹ ; ⁷ ; ¹⁷ ; ^{geoffrey_shapiro@dfci.harvard.edu}
• 关键词：dinaciclib ; CDK inhibitor ; CDK12 ; homologous recombination repair ; PARP inhibitor ; triple-negative breast cancer ; BRCA-associated breast cancer
• 刊名：Cell Reports
• 出版年：2016
• 出版时间：22 November 2016
• 年：2016
• 卷：17
• 期：9
• 页码：2367-2381
• 全文大小：5596 K
• 卷排序：17

文摘

Dinaciclib is a potent inhibitor of CDK12 and disrupts homologous recombination Residual HR is a cause of de novo PARP inhibitor resistance in BRCA-mutated cancer Dinaciclib sensitizes resistant BRCA-mutated breast cancer models to PARP inhibition In HR-deficient cancer, dinaciclib augments the response afforded by PARP inhibition