Leveraging an NQO1 Bioactivatable Drug for Tumor-Selective Use of Poly(ADP-ribose) Polymerase Inhibitors.
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ABSTRACT:
SUBMITTER: Huang X
PROVIDER: S-EPMC5161231 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
Publications
Leveraging an NQO1 Bioactivatable Drug for Tumor-Selective Use of Poly(ADP-ribose) Polymerase Inhibitors.
Huang Xiumei X Motea Edward A EA Moore Zachary R ZR Yao Jun J Dong Ying Y Chakrabarti Gaurab G Kilgore Jessica A JA Silvers Molly A MA Patidar Praveen L PL Cholka Agnieszka A Fattah Farjana F Cha Yoonjeong Y Anderson Glenda G GG Kusko Rebecca R Peyton Michael M Yan Jingsheng J Xie Xian-Jin XJ Sarode Venetia V Williams Noelle S NS Minna John D JD Beg Muhammad M Gerber David E DE Bey Erik A EA Boothman David A DA
Cancer cell 20161201 6
Therapeutic drugs that block DNA repair, including poly(ADP-ribose) polymerase (PARP) inhibitors, fail due to lack of tumor-selectivity. When PARP inhibitors and β-lapachone are combined, synergistic antitumor activity results from sustained NAD(P)H levels that refuel NQO1-dependent futile redox drug recycling. Significant oxygen-consumption-rate/reactive oxygen species cause dramatic DNA lesion increases that are not repaired due to PARP inhibition. In NQO1<sup>+</sup> cancers, such as non-smal ...[more]
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