Germline mutations in pancreatic cancer and potential new therapeutic options

Rille Pihlak; Juan W. Valle; Mairéad G. McNamara

doi:10.18632/oncotarget.17291

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Germline mutations in pancreatic cancer and potential new therapeutic options

Rille Pihlak, Juan W. Valle and Mairéad G. McNamara _

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Oncotarget. 2017; 8:73240-73257. https://doi.org/10.18632/oncotarget.17291

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Abstract

Rille Pihlak1,2, Juan W. Valle1,2 and Mairéad G. McNamara1,2

1Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, United Kingdom

2Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom

Correspondence to:

Mairéad McNamara, email: [email protected]

Keywords: pancreatic cancer, germline mutations, BRCA1, BRCA2, PARP inhibitors

Received: November 10, 2016 Accepted: April 11, 2017 Published: April 20, 2017

ABSTRACT

Due to short-lived treatment responses in unresectable disease, pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is availability of new information about germline and sporadic mutations in the deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and the expectation is that novel targeted therapies will thus be developed. A variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with the highest prevalence being BRCA1/2. Positive results have been reported with the use of targeted therapies, particularly poly (ADP-ribose) polymerase inhibitors in BRCA-mutated ovarian and breast cancers, and their use is currently being investigated in germline-mutated pancreatic cancer. The aim of this review is to provide an outline of germline DNA damage repair mutations in pancreatic cancer and their effect on the incidence, outcomes and responses to different therapeutic options.

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Germline mutations in pancreatic cancer and potential new therapeutic options

Abstract