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Therapeutic Targeting of Poly(ADP‐Ribose) Polymerase‐1 (PARP1) in Cancer: Current Developments, Therapeutic Strategies, and Future Opportunities
Author(s) -
Rajawat Jyotika,
Shukla Nidhi,
Mishra Durga Prasad
Publication year - 2017
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.21442
Subject(s) - poly adp ribose polymerase , synthetic lethality , parp1 , carcinogenesis , cancer research , dna repair , parp inhibitor , biology , cancer , polymerase , medicine , dna , genetics
Poly(ADP‐ribose) polymerase‐1 (PARP‐1) plays a central role in numerous cellular processes including DNA repair, replication, and transcription. PARP interacts directly, indirectly or via PARylation with various oncogenic proteins and regulates several transcription factors thereby modulating carcinogenesis. Therapeutic inhibition of PARP is therefore perceived as a promising anticancer strategy and a number of PARP inhibitors (PARPi) are currently under development and clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the concept of synthetic lethality in cancer therapeutics. Preclinical and clinical studies have shown the potential of PARPi as chemopotentiator, radiosensitizer, or as adjuvant therapeutic agents. Recent studies have shown that PARP‐1 could be either oncogenic or tumor suppressive in different cancers. PARP inhibitor resistance is also a growing concern in the clinical setting. Recently, changes in the levels of PARP‐1 activity or expression in cancer patients have provided the basis for consideration of PARP‐1 regulatory proteins as potential biomarkers. This review focuses on the current developments related to the role of PARP in cancer progression, therapeutic strategies targeting PARP‐associated oncogenic signaling, and future opportunities in use of PARPi in anticancer therapeutics.