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BRCA Mutations in Pancreas Cancer: Spectrum, Current Management, Challenges and Future Prospects

Authors Wong W, Raufi AG, Safyan RA, Bates SE, Manji GA

Received 14 January 2020

Accepted for publication 4 April 2020

Published 23 April 2020 Volume 2020:12 Pages 2731—2742

DOI https://doi.org/10.2147/CMAR.S211151

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


Winston Wong,1 Alexander G Raufi,1,2 Rachael A Safyan,1 Susan E Bates,1,3 Gulam A Manji1,4

1Division of Hematology and Oncology, Columbia University Medical Center and New York Presbyterian Hospital Herbert Irving Pavilion, New York, NY 10032, USA; 2Division of Hematology-Oncology, Lifespan Cancer Institute, Warren-Alpert Medical School of Brown University, Providence, RI, USA; 3Division of Hematology and Oncology, James J. Peters Veterans Affairs Medical Center, The Bronx, NY 10468, USA; 4Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center and New York Presbyterian Hospital Herbert Irving Pavilion, New York, NY 10032, USA

Correspondence: Winston Wong
Division of Hematology and Oncology, Columbia University Medical Center and New York Presbyterian Hospital, Milstein Hospital Building, 6 Garden North, Rm 6-435 177 Fort Washington Ave, New York, NY 10032, USA
Tel +646-675-8254
Email ww2539@cumc.columbia.edu

Abstract: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease to treat. Despite advances in surgical techniques, radiation, and medical therapies, the 5-year survival rate remains below 9%. Over the past decade, the genomic landscape of PDAC has been well studied and BRCA mutations have emerged as a target for the development of more effective therapies. Alterations in germline BRCA and PALB2 are detected in approximately 5– 9% of patients with PDAC and can lead to homologous repair deficiency (HRD). PDAC with HRD is more susceptible to cytotoxic agents, such as platinum salts and topoisomerase inhibitors, that cause DNA damage. Furthermore, PARP inhibitors have emerged as an effective non-cytotoxic approach to treating HRD-PDAC. In addition to BRCA and PALB2, germline mutations in other genes involved in the homologous DNA repair pathway – such as ATM and RAD51 – are potential targets, as are patients with the “BRCAness” phenotype and somatic mutations in the DNA repair pathway. Given the clinical implications of germline mutation related HRD in PDAC, universal germline testing is now recommended. In this review, we will discuss current and emerging biomarkers for HRD in PDAC, treatments, and the challenges associated with them.

Keywords: pancreas cancer, clinical trials, BRCA

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