DNA Topoisomerase I-Targeted Therapy for Breast Cancer

Abstract

The specific aim of this work is to develop camptothecin (CPT) analogs for treatment of women with breast cancer. We evaluated these analogs using three biochemical tests: (1) inhibition of growth of breast cancer cells, (2) induction of topoisomerase I-mediated cleavage of DNA, and (3) reversal of DNA cleavage. Our results indicate that the % 1O,11- methylenedioxy CPT analog was effective in all three tests. Further, this analog was effective against MX-1 and MDA-231 human breast cancer xenografts growing in nude mice. The 10,11- methylenedioxy analog appears to be the best choice among the analogs examined, and we are currently pursuing moving this compound into clinical studies.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 1998
Accession Number
ADA350914

Entities

People

  • Daniel D. Von Hoff

Tags

DTIC Thesaurus Topics

  • Alkaloids
  • Analogs
  • Animals
  • Antineoplastic Agents
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Chemistry
  • Chemotherapy
  • Culture Techniques
  • Diseases And Disorders
  • Inhibition
  • Materials
  • Neoplasms
  • Statistical Analysis
  • Xenografts

Readers

  • Breast cancer cell signaling and growth regulation.
  • Cellular and Molecular Pathways of Apoptosis.
  • Geotechnical Engineering.