Homologous Repair-Deficient Pancreatic Cancer: Refined Targeting of DNA Damage Response is an Effective Therapeutic Strategy.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a high mortality rate. While up to 20% of PDAC patients harbor mutations in genes involved in homologous recombination (HR) repair, only 5% of germline BRCA1/2 mutation carriers have an approved treatment option with the PARP inhibitor (PARPi) olaparib. Characterizing HR-deficient (HRD) genotypes beyond gBRCA1/2 that are susceptible to PARPi has potential to substantially broaden the eligible patient population, and defining the optimal inhibitor may further optimize treatment strategies to advance personalized medicine in PDAC.

Objective

Our previous preclinical work showed synthetic lethality of a multi-pronged DNA damage repair interference strategy using the PARPi olaparib, ATR inhibitor

SUBMITTER: Beutel AK 

PROVIDER: S-EPMC12463693 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature