Preclinical Models for Evaluating Topoisomerase I-Targeted Drugs

  • Aarti S. Juvekar
  • Joyce Thompson
  • Clinton F. Stewart
  • Peter J. Houghton
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Type I and II DNA topoisomerases are the targets for numerous clinically efficacious antitumor agents. Over the last decade, considerable effort has been expended in developing camptothecin (CPT) derivatives that selectively target DNA topoisomerase I (TOP-I) (1). The prodrug irinotecan (CPT-11) is approved for treatment of colon carcinoma and has demonstrated significant activity against numerous other cancers in adults and children. Topotecan is approved for treatment of platinum- or taxane-resistant ovarian carcinoma and has demonstrated broad-spectrum activity (2). Other analogs are in clinical development, such as D5198f and the homocamptothecins and liposomal formulations of CPT derivatives, and offer the potential for prolonged plasma exposures.


Systemic Exposure Breast Cancer Resistance Protein Human Tumor Xenograft Lactone Form Camptothecin Analog 
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Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Aarti S. Juvekar
    • 1
    • 2
  • Joyce Thompson
    • 3
  • Clinton F. Stewart
    • 4
  • Peter J. Houghton
    • 1
  1. 1.Department of Molecular PharmacologySt. Jude Children’s Research HospitalMemphis
  2. 2.Cancer Research InstituteParel, BombayIndia
  3. 3.Department of Hematology/OncologySt. Jude Children’s Research HospitalMemphis
  4. 4.Department of Pharmaceutical SciencesSt. Jude Children’s Research HospitalMemphis

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