Leveraging an NQO1 Bioactivatable Drug for Tumor-Selective Use of Poly(ADP-ribose) Polymerase Inhibitors

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• 作者：Xiumei Huang¹ ; Edward A. Motea¹ ; Zachary R. Moore¹ ; Jun Yao¹ ; Ying Dong¹ ; Gaurab Chakrabarti¹ ; Jessica A. Kilgore² ; Molly A. Silvers¹ ; Praveen L. Patidar¹ ; Agnieszka Cholka¹ ; Farjana Fattah¹ ; Yoonjeong Cha³ ; Glenda G. Anderson⁴ ; Rebecca Kusko³ ; Michael Peyton⁵ ; Jingsheng Yan⁶ ; Xian-Jin Xie⁶ ; Venetia Sarode⁷ ; Noelle S. Williams² ; John D. Minna⁵ ; Muhammad Beg⁵ ; David E. Gerber⁵ ; Erik A. Bey⁸ ; ^{erik.bey@hsc.wvu.edu} ; David A. Boothman¹ ; ⁹ ; ^{david.boothman@utsouthwestern.edu}
• 关键词：NQO1 ; PARP1 ; β-lapachone ; NQO1 bioctivatable drugs ; Rucaparib ; Olaparib ; ARQ761 ; ROS ; NSCLC ; PDA ; combination chemotherapy ; synthetic lethality
• 刊名：Cancer Cell
• 出版年：2016
• 出版时间：12 December 2016
• 年：2016
• 卷：30
• 期：6
• 页码：940-952
• 全文大小：4031 K
• 卷排序：30

文摘

Solid cancers overexpress NQO1, with low catalase levels, reverse of normal tissue β-Lapachone kills independent of oncogenic driver or passenger mutations Synergy with PARP inhibitors and β-lapachone is NQO1 dependent PARP inhibitors + β-lap induce DNA lesions, block repair, and cause apoptosis