Germline mutations in pancreatic cancer and potential new therapeutic options

Rille Pihlak; Juan Valle; Mairead Mcnamara

doi:10.18632/oncotarget.17291

Germline mutations in pancreatic cancer and potential new therapeutic options

Rille Pihlak, Juan Valle, Mairead Mcnamara

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Oncotarget
DOIs	https://doi.org/10.18632/oncotarget.17291
Publication status	Published - 20 Apr 2017

Keywords

pancreatic cancer
germline mutations
BRCA1, BRCA2, PARP inhibitors

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.17291Licence: CC BY

Cite this

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title = "Germline mutations in pancreatic cancer and potential new therapeutic options",

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. ",

keywords = "pancreatic cancer , germline mutations , BRCA1, BRCA2, PARP inhibitors",

author = "Rille Pihlak and Juan Valle and Mairead Mcnamara",

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language = "English",

journal = "Oncotarget",

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T1 - Germline mutations in pancreatic cancer and potential new therapeutic options

AU - Pihlak, Rille

AU - Valle, Juan

AU - Mcnamara, Mairead

PY - 2017/4/20

Y1 - 2017/4/20

N2 - 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.

AB - 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.

KW - pancreatic cancer

KW - germline mutations

KW - BRCA1, BRCA2, PARP inhibitors

U2 - 10.18632/oncotarget.17291

DO - 10.18632/oncotarget.17291

M3 - Article

SN - 1949-2553

JO - Oncotarget

JF - Oncotarget

ER -

Germline mutations in pancreatic cancer and potential new therapeutic options

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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