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September 29, 2025Cancer Research

Abstract B093: Investigating mechanisms of PARP inhibitor resistance in homologous recombination deficient PDAC using patient-derived organoid models

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Authors

AGAustin L. GoodSOSean Timothy Francis O’ConnorTBTimour Baslan

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Overview

The analysis reveals multiple resistance mechanisms in BR-PDAC organoids, indicating complex BRCA2 involvement in homologous recombination.

Key Points

  • PARP inhibitor resistance was linked to novel BRCA2 deletion variants in patient-derived organoids, emphasizing genetic complexity.
  • Whole genome sequencing identified deletions affecting BRCA2 splice regions, contributing to the organoids' resistance mechanisms.
  • CRISPR interference experiments revealed that depleting BRCA2 enhanced PARP inhibitor sensitivity, suggesting partial restoration of its function.
  • The findings highlight the utility of patient-derived organoids in understanding unique genetic variants involved in PARP inhibitor resistance.

Cite This Study

Good et al. (2025) studied this question.

synapsesocial.com/papers/68da58dcc1728099cfd1145fhttps://doi.org/10.1158/1538-7445.pancreatic25-b093
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract A031: Identification of therapeutic vulnerabilities in the subset of pancreatic ductal adenocarcinoma (PDAC) with homologous recombination deficiency2024
  2. 2Abstract 393: Uncovering mechanisms of PARP inhibitor resistance in IDH1-mutant cancers via serial tumor transplantation and genome wide CRISPR-Cas9 knockout screen.2026
  3. 3Abstract 2177: Characterization of a panel of PDX models derived from PARP inhibitors pretreated breast and ovarian cancer patients for therapeutic evaluation.2026
  4. 4Abstract 538: Establishment of PARP inhibitor-induced resistant patient-derived ovarian cancer xenograft models2024
  5. 5Abstract 240: Allele-specific sensitization of pancreatic ductal adenocarcinoma to PARP inhibition via adenine base editing.2026