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Germline Aberrations in Pancreatic Cancer: Implications for Clinical Care

Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK
Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK
NHS Greater Glasgow and Clyde, Glasgow G4 0SF, UK
Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California Davis, Davis, CA 95616, USA
Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA
General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, 37134 Verona, Italy
Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK
South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, NSW 2170, Australia
Author to whom correspondence should be addressed.
Academic Editor: Murray Korc
Cancers 2022, 14(13), 3239;
Received: 9 June 2022 / Revised: 27 June 2022 / Accepted: 28 June 2022 / Published: 30 June 2022
(This article belongs to the Collection Aberrant Signaling Pathways in Pancreatic Cancer)
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis and represents a major public health issue, as both its incidence and mortality are expecting to increase steeply over the next years. Effective screening strategies are lacking, and most patients are diagnosed with unresectable disease precluding the only chance of cure. Therapeutic options for advanced disease are limited, and the treatment paradigm is still based on chemotherapy, with a few rare exceptions to targeted therapies. Germline variants in cancer susceptibility genes—particularly those involved in mechanisms of DNA repair—are emerging as promising targets for PDAC treatment and prevention. Hereditary PDAC is part of the spectrum of several syndromic disorders, and germline testing of PDAC patients has relevant implications for broad cancer prevention. Germline aberrations in BRCA1 and BRCA2 genes are predictive biomarkers of response to poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitor olaparib and platinum-based chemotherapy in PDAC, while mutations in mismatch repair genes identify patients suitable for immune checkpoint inhibitors. This review provides a timely and comprehensive overview of germline aberrations in PDAC and their implications for clinical care. It also discusses the need for optimal approaches to better select patients for PARP inhibitor therapy, novel therapeutic opportunities under clinical investigation, and preclinical models for cancer susceptibility and drug discovery. View Full-Text
Keywords: germline; pancreatic cancer; BRCA; PARP inhibitors; precision prevention; familial pancreatic cancer germline; pancreatic cancer; BRCA; PARP inhibitors; precision prevention; familial pancreatic cancer
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MDPI and ACS Style

Casolino, R.; Corbo, V.; Beer, P.; Hwang, C.-i.; Paiella, S.; Silvestri, V.; Ottini, L.; Biankin, A.V. Germline Aberrations in Pancreatic Cancer: Implications for Clinical Care. Cancers 2022, 14, 3239.

AMA Style

Casolino R, Corbo V, Beer P, Hwang C-i, Paiella S, Silvestri V, Ottini L, Biankin AV. Germline Aberrations in Pancreatic Cancer: Implications for Clinical Care. Cancers. 2022; 14(13):3239.

Chicago/Turabian Style

Casolino, Raffaella, Vincenzo Corbo, Philip Beer, Chang-il Hwang, Salvatore Paiella, Valentina Silvestri, Laura Ottini, and Andrew V. Biankin. 2022. "Germline Aberrations in Pancreatic Cancer: Implications for Clinical Care" Cancers 14, no. 13: 3239.

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