Patient-derived xenograft models of BRCA-associated pancreatic cancers

Talia Golan*, Dikla Atias, Chani Stossel, Maria Raitses-Gurevich

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease. The majority of patients diagnosed at an advanced, metastatic stage, and poor overall survival rates. The most clinically meaningful subtype obtained from PDAC genomic classification is represented by unstable genomes, and co-segregated with inactivation of DNA damage repair genes, e.g., Breast cancer 1/2 (BRCA1/2). The FDA and EMA has recently approved olaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor, as a maintenance strategy for platinum-sensitive advanced PDAC patients with BRCA mutations. However, susceptibility to treatment varies, and resistance may develop. Resistance can be defined as innate or acquired resistance to platinum/PARP-inhibition. Patient-derived xenograft (PDX) models have been utilized in cancer research for many years. We generated a unique PDX model, obtained from BRCA-associated PDAC patients at distinct time points of the disease recapitulating the different clinical scenario. In this review we discuss the relevant PDX-derived models for investigating BRCA-associated PDAC and drug development.

Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalAdvanced Drug Delivery Reviews
Volume171
DOIs
StatePublished - Apr 2021

Keywords

  • BRCA 1/2
  • Drug development
  • PARP inhibitors
  • PDX models
  • Pancreatic ductal adenocarcinoma
  • Platinum agents
  • Resistance
  • Response

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