Poly(ADP-Ribose) Polymerase Inhibitors in Pancreatic Cancer: A New Treatment Paradigms and Future Implications
1
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
2
Department of Medicine/Division of GI Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(12), 1980; https://doi.org/10.3390/cancers11121980
Received: 1 November 2019 / Revised: 30 November 2019 / Accepted: 6 December 2019 / Published: 9 December 2019
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy. Most of the patients of PDAC present at later stages of disease and have a five-year survival rate of less than 10%. About 5–10% PDAC cases are hereditary in nature and have DNA damage repair (DDR) mutations such as BRCA 1 and 2. Besides having implications on screening and prevention strategies, these mutations can confer sensitivity to platinum-based therapies and determine eligibility for poly(ADP-ribose) polymerase inhibitors (PARPi). In the presence of DDR mutations and PARPi, the cells are unable to utilize the error-free process of homologous recombination repair, leading to accumulation of double stranded DNA breaks and cell death eventually. Various PARPi are in clinical development in PDAC in different subgroup of patients as monotherapies and in combination with other therapeutics. This review would focus on the mechanism of action of PARPi, history of development in PDAC, resistance mechanisms and future directions.
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MDPI and ACS Style
Gupta, M.; Iyer, R.; Fountzilas, C. Poly(ADP-Ribose) Polymerase Inhibitors in Pancreatic Cancer: A New Treatment Paradigms and Future Implications. Cancers 2019, 11, 1980. https://doi.org/10.3390/cancers11121980
AMA Style
Gupta M, Iyer R, Fountzilas C. Poly(ADP-Ribose) Polymerase Inhibitors in Pancreatic Cancer: A New Treatment Paradigms and Future Implications. Cancers. 2019; 11(12):1980. https://doi.org/10.3390/cancers11121980
Chicago/Turabian StyleGupta, Medhavi; Iyer, Renuka; Fountzilas, Christos. 2019. "Poly(ADP-Ribose) Polymerase Inhibitors in Pancreatic Cancer: A New Treatment Paradigms and Future Implications" Cancers 11, no. 12: 1980. https://doi.org/10.3390/cancers11121980
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