Trapping Poly(ADP-Ribose) Polymerase

The Journal of Pharmacology and Experimental Therapeutics
Yuqiao ShenBing Wang

Abstract

Recent findings indicate that a major mechanism by which poly(ADP-ribose) polymerase (PARP) inhibitors kill cancer cells is by trapping PARP1 and PARP2 to the sites of DNA damage. The PARP enzyme-inhibitor complex "locks" onto damaged DNA and prevents DNA repair, replication, and transcription, leading to cell death. Several clinical-stage PARP inhibitors, including veliparib, rucaparib, olaparib, niraparib, and talazoparib, have been evaluated for their PARP-trapping activity. Although they display similar capacity to inhibit PARP catalytic activity, their relative abilities to trap PARP differ by several orders of magnitude, with the ability to trap PARP closely correlating with each drug's ability to kill cancer cells. In this article, we review the available data on molecular interactions between these clinical-stage PARP inhibitors and PARP proteins, and discuss how their biologic differences might be explained by the trapping mechanism. We also discuss how to use the PARP-trapping mechanism to guide the development of PARP inhibitors as a new class of cancer therapy, both for single-agent and combination treatments.

References

Dec 13, 1979·Nature·H Juarez-SalinasM K Jacobson
Mar 26, 1992·Nature·M S Satoh, T Lindahl
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J Nitiss, J C Wang
Feb 7, 1980·Nature·B W DurkaczS Shall
Jul 17, 1995·Biochemical and Biophysical Research Communications·E A MirandaJ M de Murcia
Jan 1, 1993·European Journal of Clinical Pharmacology·B E Wiholm, M Myrhed
Jun 11, 1999·The Journal of Biological Chemistry·J C AméG de Murcia
Aug 16, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Yves PommierGary S. Laco
Oct 25, 2003·Oncogene·Zeshaan A Rasheed, Eric H Rubin
Jan 8, 2004·Journal of the National Cancer Institute·Christopher R CalabreseNicola J Curtin
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Valérie SchreiberGilbert de Murcia
Aug 8, 2006·Progress in Nucleic Acid Research and Molecular Biology·Yves PommierChristophe Redon
Dec 16, 2006·Current Medicinal Chemistry·G L BerettaF Zunino
Nov 21, 2007·The Journal of Biological Chemistry·Jean-François HainceGuy G Poirier
Dec 7, 2007·The Journal of Biological Chemistry·Marie-France LangelierJohn M Pascal
May 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jann N SarkariaWolfgang Wick
Jun 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Darren J BurgessMichael T Hemann
Jul 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alan Ashworth
Apr 30, 2009·Journal of the National Cancer Institute·F P O'MalleyK I Pritchard
Jun 26, 2009·Bioorganic & Medicinal Chemistry Letters·Julie MiyashiroThomas D Penning
Mar 5, 2010·Nature Reviews. Cancer·Michèle RouleauGuy G Poirier
Apr 7, 2010·Journal of Medicinal Chemistry·Dana V Ferraris
Apr 22, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter C FongStan B Kaye
Jun 11, 2010·Chemistry & Biology·Yves PommierChristophe Marchand
Jun 17, 2010·Cancer Research·Ponnari GottipatiThomas Helleday

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Citations

Dec 3, 2015·Molecular Cell·Sebastian EustermannDavid Neuhaus
Mar 31, 2016·British Journal of Cancer·Jessica S BrownTimothy A Yap
Jun 17, 2016·Molecular & Cellular Oncology·Antonella SistiguIlio Vitale
Oct 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·K VeskimäeJ Mäenpää
Nov 1, 2016·Science Translational Medicine·Yves PommierJohann de Bono
Nov 15, 2016·Expert Opinion on Therapeutic Patents·Zigao YuanYuyang Jiang
Jan 15, 2017·Seminars in Cell & Developmental Biology·Caleb DulaneyEddy S Yang
Jun 16, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M Catherine PietanzaLauren Averett Byers
Oct 2, 2015·ChemMedChem·Daniela PasseriAntonio Macchiarulo
Aug 9, 2018·ELife·Johannes RudolphKarolin Luger
Oct 13, 2018·Expert Opinion on Pharmacotherapy·Giulia BaciarelloKarim Fizazi
Oct 6, 2018·Molecular Oncology·Sabine Hombach-KlonischThomas Klonisch
Jan 25, 2019·International Journal of Cancer. Journal International Du Cancer·Hua-Dong ChenZe-Hong Miao
Sep 13, 2019·Expert Review of Proteomics·Marilyne LabrieGordon B Mills
Feb 8, 2020·Genes & Development·Dea Slade
Jan 9, 2020·Journal of Cellular Physiology·Federica TomaoPierluigi Benedetti Panici
Dec 22, 2017·Oncotarget·Eva KukoljDea Slade
Dec 1, 2017·Cancer Chemotherapy and Pharmacology·Xiaojun LiuWilliam Plunkett
Jun 23, 2020·Expert Opinion on Emerging Drugs·Elizabeth K Lee, Ursula A Matulonis
Jun 13, 2020·Cancers·Florent Peyraud, Antoine Italiano
Oct 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rachel AbbottsFeyruz V Rassool
Jul 12, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lena J McLaughlinFeyruz V Rassool
Aug 28, 2020·F1000Research·David C Swinney, Jonathan A Lee
Aug 30, 2020·Scientific Reports·Praveen L PatidarFarjana J Fattah
Apr 5, 2020·International Journal of Molecular Sciences·Dmitry NilovVasily M Studitsky
Oct 9, 2015·Current Opinion in Oncology·Geraldine OʼSullivan CoyneShivaani Kummar
Jan 13, 2017·Drugs·Geraldine O'Sullivan CoyneJames H Doroshow
Apr 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Benjamin D DicksonMichael P Hay

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