Targeting the UPR to Circumvent Endocrine Resistance in Breast Cancer

Abstract

In this Idea Expansion (IDEX) Grant, we propose that targeting IRE1 in endocrine resistant breast cancer cells with N-(4-Phenoxy-phenyl)-2-(5-pyridin-3-yl-2H-[1,2,4]triazol-3-ylsulfanyl)-acetamide (NPPTA; lead compound), or itsanalogs, will block pro-survival signaling from the UPR and prevent survival (via pro-survival autophagy and aninhibition of apoptosis). We hypothesize that these effects will be mediated in part by the inhibition of XBP1 splicing and its ability to regulate BCL2 family members and NFB. Furthermore, a combination of NPPTA and AEs will interact synergistically to selectively kill AE resistant breast cancer cells in vitro and in vivo.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2015
Accession Number
AD1007758

Entities

People

  • Robert Clarke

Organizations

  • Georgetown University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • African Americans
  • Apoptosis
  • Autophagy
  • Breast Cancer
  • Cell Physiological Processes
  • Gene Expression
  • Inhibition
  • Lead Compounds
  • Neoplasms
  • Proteins
  • Resistance
  • Small Molecules
  • Students
  • Surface Plasmon Resonance
  • Surface Plasmons
  • Survival
  • Targeting

Fields of Study

  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Biology and Genetics