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Mol Cell. 2015 Jun 18;58(6):925-34. doi: 10.1016/j.molcel.2015.04.016.

Chromatin to Clinic: The Molecular Rationale for PARP1 Inhibitor Function.

Author information

1
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA.
2
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK.
3
Institute for Precision Medicine of Weill Cornell Medical College and NewYork-Presbyterian Hospital; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College; Department of Urology, Weill Cornell Medical College; Meyer Cancer Center of Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10021, USA.
4
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Department of Urology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: karen.knudsen@jefferson.edu.

Abstract

Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have potential clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed.

PMID:
26091341
PMCID:
PMC4487541
DOI:
10.1016/j.molcel.2015.04.016
[Indexed for MEDLINE]
Free PMC Article

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