Is Altered Metabolism and Elimination Responsible for Tamoxifen Resistance?

Abstract

The development of resistance to tamoxifen is a pressing issue in breast cancer management, as this typically results in poor prognosis and an increased chance of patient relapse. Tamoxifen is metabolized by the cytochrome P450s, and these products may then be further metabolized to glucuronide conjugates, which can ultimately by eliminated from tumor cells by transport proteins including MRP1 and MPR3. We hypothesized that we could use specific enzyme inhibitors of the metabolizing and transport enzymes to increase tamoxifen concentrations in MCF7 breast cancer cells. The results demonstrated that several of the inhibitors could indeed reduce the amount and type of tamoxifen metabolites formed. In addition, one of the inhibitors increased the amount of tamoxifen retained in the cells. These compounds may be good candidates to design adjuvant therapies for breast cancer treatment.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2002
Accession Number
ADB282133

Entities

People

  • Charles D. Rice
  • Lisa J. Bain

Organizations

  • Clemson University

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Anti-Bacterial Agents
  • Biomedical Research
  • Breast Cancer
  • Cells
  • Cytochromes
  • Elimination
  • Enzyme Inhibitors
  • Government Procurement
  • Governments
  • Inhibitors
  • Metabolism
  • Metabolites
  • Microsomes
  • Neoplasms
  • Resistance
  • Transport Ships

Readers

  • Molecular and Cellular Biochemistry
  • Oncology (Cancer Research).