Accession Number:

AD1095203

Title:

Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers

Descriptive Note:

Technical Report,30 Sep 2018,29 Sep 2019

Corporate Author:

The Geneva Foundation Tacoma United States

Personal Author(s):

Report Date:

2019-10-01

Pagination or Media Count:

19.0

Abstract:

PolyADP-ribose polymerase PARP inhibition provides a promising therapeutic modality for targeting homologous recombination HR deficient tumors such as BRCA1 and BRCA2-mutated triple negative breast cancers TNBCs. Although PARP inhibitors have shown activity in the BRCA-associated TNBCs, several of these tumors develop de novo as well as acquired PARP inhibitor PARPi resistance. Besides attenuation in intracellular uptake of drugs, the only known mechanism that drives chemotherapy resistance of BRCA12-deficient cancers is through the restoration of HR. Recent studies from our laboratories Nussenzweig and DAndrea indicate that deregulation of pathways that promote extensive degradation of nascent DNA strands and alternative end-joining Alt-EJ can render BRCA12-deficient cells resistant to PARPi in a HR-independent manner. The objective of our project is to collaboratively test the hypothesis that complex processes involving Alt-EJ or replication fork stability promote survival and drives resistance to chemotherapy.

Subject Categories:

  • Medicine and Medical Research
  • Pharmacology
  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE