A paradigm for the treatment of prostate cancer bone metastases based on an understanding of tumor cell–microenvironment interactions

Authors

  • Robert D. Loberg,

    Corresponding author
    1. Departments of Urology and Internal Medicine, University of Michigan Urology Center, The University of Michigan, Ann Arbor, Michigan
    • University of Michigan Urology Center, 7431 CCGC, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0946.
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  • Bishoy A. Gayed,

    1. Departments of Urology and Internal Medicine, University of Michigan Urology Center, The University of Michigan, Ann Arbor, Michigan
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  • Karin B. Olson,

    1. Departments of Urology and Internal Medicine, University of Michigan Urology Center, The University of Michigan, Ann Arbor, Michigan
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  • Kenneth J. Pienta

    1. Departments of Urology and Internal Medicine, University of Michigan Urology Center, The University of Michigan, Ann Arbor, Michigan
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Abstract

The pliability of cancer cells to mutate into several different phenotypes in an attempt to find one that will survive and colonize at the metastatic site is a tremendous “hurdle” to overcome in designing novel cancer therapeutics. New targets of therapy are essential if we are to effectively overcome the evasiveness of cancer. The interaction between the tumor cell and the surrounding microenvironment creates a vicious cycle that perpetuates disease survival and progression. The future of cancer therapy resides in the ability to focus on the recruited and exploited relationships of the cancer cell with the host environment. These therapies target cancer cell growth early and interrupt the vicious cycle that is created by the tumor cells interacting with bone components by inhibiting osteoclasts, osteoblasts, stromal cells, and endothelial cells. They alter the bone microenvironment, creating a hostile “soil” that prevents the “seed” from developing into bone metastases and represent a potential new platform for the development of prostate cancer therapeutics. © 2005 Wiley-Liss, Inc.

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