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Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance

Author

Listed:
  • Thomas Boehm

    (Dana Farber Cancer Center)

  • Judah Folkman

    (Dana Farber Cancer Center
    Cellular Biology)

  • Timothy Browder

    (Dana Farber Cancer Center
    Dana Farber Cancer Center
    Children's Hospital, Dana Farber Cancer Center
    Pediatrics)

  • Michael S. O'Reilly

    (Dana Farber Cancer Center
    Joint Center for Radiation Therapy, Harvard Medical School)

Abstract

Acquired drug resistance is a major problem in the treatment of cancer. Of the more than 500,000 annual deaths from cancer in the United States1, many follow the development of resistance to chemotherapy. The emergence of resistance depends in part on the genetic instability, heterogeneity and high mutational rate of tumour cells2. In contrast, endothelial cells are genetically stable, homogenous and have a low mutational rate. Therefore, antiangiogenic therapy directed against a tumour's endothelial cells should, in principle, induce little or no drug resistance. Endostatin3, a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy. These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor. An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.

Suggested Citation

  • Thomas Boehm & Judah Folkman & Timothy Browder & Michael S. O'Reilly, 1997. "Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance," Nature, Nature, vol. 390(6658), pages 404-407, November.
    • Handle: RePEc:nat:nature:v:390:y:1997:i:6658:d:10.1038_37126
    DOI: 10.1038/37126
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    Cited by:

    1. U. Ledzewicz & H. Schättler, 2012. "Multi-input Optimal Control Problems for Combined Tumor Anti-angiogenic and Radiotherapy Treatments," Journal of Optimization Theory and Applications, Springer, vol. 153(1), pages 195-224, April.
    2. Thomas Schuster, 2003. "Meta-Communication and Market Dynamics. Reflexive Interactions of Financial Markets and the Mass Media," Finance 0307014, University Library of Munich, Germany.
    3. A. Nowakowski & A. Popa, 2013. "A Dynamic Programming Approach for Approximate Optimal Control for Cancer Therapy," Journal of Optimization Theory and Applications, Springer, vol. 156(2), pages 365-379, February.

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