Physiological Stress-Induced Drug Resistance and Its Reversal

Abstract

Physiological stress conditions associated with solid tumor play a role in chemotherapeutic resistance. Treatment with hypoxia or chemical stress agents causes EMT6 mouse mammary tumor cells to develop resistance to etoposide and teniposide, prototypic topoisomerase II inhibitors. We have shown that NFkB activation plays an important role in stress induced resistance and have used gene expression technology to identify potential genes responsible for the resistant phenotype. One pathway identified involves TGF-beta, PDGFRalpha and MEKl/2 which we have shown to be directly linked to NFkB activation in EMT6 mouse mammary tumor cells. Further additional potential genes involved in the reversal of resistance have been identified. Our data suggest that interrupting the NFkB pathway may be a useful strategy to improve the efficacy of topoisomerase IT inhibitors.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2002
Accession Number
ADA408700

Entities

People

  • Katherine A. Kennedy

Organizations

  • George Washington University

Tags

DTIC Thesaurus Topics

  • Antineoplastic Agents
  • Biological Factors
  • Biomedical And Dental Materials
  • Breast Cancer
  • Carrier Proteins
  • Cell Physiological Processes
  • Chemistry
  • Chemotherapy
  • Growth Factors
  • Health Services
  • Indicator Dyes
  • Peptide Growth Factors
  • Peptides
  • Pharmacology
  • Polymeric Films
  • Proteins
  • Stress (Physiology)

Fields of Study

  • Biology
  • Medicine

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Oncology (Cancer Research).