Identification of a PARP Inhibitor Sensitivity Signature in Breast Cancer Using a Novel Transcription Factor Activity Array

Abstract

A system for the large scale, dynamic quantification of transcription factor activity was applied to investigate the mechanism of action for PARP inhibitors. Of the 34 TFs investigated, 15 had differential activity in the presence of the PARP inhibitor olaparib. A few of the TF had differential activity in BRCA1-wild type and BRCA1-null cells. This differential activity may underlie why some patients respond whereas others are resistant. In addition, five PARP-1 inhibitor resistant clones were established from BRCA1-null type cells. Cell array analysis from these clones will provide us valuable insights into addressing the occurrence of resistance. We are continuing to investigate these factors to identify whether targeting these additional pathways can increase the efficacy or reduce resistance to PARP inhibitors.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2012
Accession Number
ADA559941

Entities

People

  • Lonnie D. Shea

Organizations

  • Northwestern University

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Carcinoma
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Department Of Defense
  • Drug Resistance
  • Inhibitors
  • Medical Personnel
  • Molecules
  • Neoplasms
  • Ovarian Cancer
  • Proteins
  • Resistance
  • Transcription Factors

Readers

  • Molecular and genetic basis of cancer.
  • Oncology