Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer

DOI Web Site 45 Citations
  • Chris Tran
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Samedy Ouk
    Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Nicola J. Clegg
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Yu Chen
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Philip A. Watson
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Vivek Arora
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • John Wongvipat
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Peter M. Smith-Jones
    Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Dongwon Yoo
    Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Andrew Kwon
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Teresa Wasielewska
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Derek Welsbie
    Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Charlie Degui Chen
    Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Celestia S. Higano
    Division of Oncology, Departments of Medicine and Urology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Tomasz M. Beer
    OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
  • David T. Hung
    Medivation, Inc., 201 Spear Street, San Francisco, CA 94105, USA.
  • Howard I. Scher
    Genitourinary Oncology Service, Division of Solid Tumor Oncology and Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Michael E. Jung
    Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Charles L. Sawyers
    Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Abstract

<jats:title>A Second Act for Antiandrogens</jats:title> <jats:p> Men with advanced prostate cancer are often treated with antiandrogens; drugs that inhibit the activity of male hormones, such as testosterone, that help drive tumor growth. Many of these drugs act by functionally disrupting the androgen receptor (AR), a transcriptional regulator of cell proliferation, but tumors eventually become resistant to the drugs by expressing higher levels of the AR. <jats:bold> Tran <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="787" related-article-type="in-this-issue" vol="324" xlink:href="10.1126/science.1168175">787</jats:related-article> , published online 9 April) have developed a “second-generation” antiandrogen, a thiohydantoin called MDV3100, which binds the AR with high affinity. MDV3100 retains its anticancer activity in cell culture and in mouse models even when AR levels are elevated. The drug appears to act both by inhibiting translocation of the AR into the nucleus and by reducing its transcriptional activity. MDV3100 is being tested in patients with advanced prostate cancer, the first group of which have shown a decline in blood levels of a marker of cancer growth, prostate-specific antigen. </jats:p>

Journal

  • Science

    Science 324 (5928), 787-790, 2009-05-08

    American Association for the Advancement of Science (AAAS)

Citations (45)*help

See more

Details 詳細情報について

Report a problem

Back to top