Strategies for the Management of Patients with Pancreatic Cancer with PARP Inhibitors

Talia Golan*, Maria Raitses-Gurevich, Tamar Beller, James Carroll, Jonathan R. Brody

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

A subset of patients with pancreatic adenocarcinomas (PDAC) harbor mutations that are exploitable in the context of DNA-damage response and repair (DDR) inhibitory strategies. Between 8–18% of PDACs harbor specific mutations in the DDR pathway such as BRCA1/2 mutations, and a higher prevalence exists in high-risk populations (e.g., Ashkenazi Jews). Herein, we will review the current trials and data on the treatment of PDAC patients who harbor such mutations and who appear sensitive to platinum and/or poly ADP ribose polymerase inhibitor (PARPi) based therapies due to a concept known as synthetic lethality. Although this current best-in-class precision treatment shows clinical promise, the specter of resistance limits the extent of therapeutic responses. We therefore also evaluate promising pre-clinical and clinical approaches in the pipeline that may either work with existing therapies to break resistance or work separately with combination therapies against this subset of PDACs.

Original languageEnglish
Title of host publicationCancer Treatment and Research
PublisherSpringer Science and Business Media Deutschland GmbH
Pages125-142
Number of pages18
DOIs
StatePublished - 2023

Publication series

NameCancer Treatment and Research
Volume186
ISSN (Print)0927-3042
ISSN (Electronic)2509-8497

Keywords

  • BRCA1/2
  • Clinical trials
  • DNA damage repair
  • HuR
  • Novel therapies
  • PARG
  • PARP inhibitor
  • Pancreatic cancer
  • Pancreatic ductal adenocarcinoma
  • Therapeutic resistance

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