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Metastasis and bone loss: Advancing treatment and prevention

  • Robert E. Coleman
    Correspondence
    Corresponding author. Tel.: +44 114 226 5213; fax: +44 114 226 5364.
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    Yorkshire Cancer Research Professor of Medical Oncology, Academic Unit of Clinical Oncology, Weston Park Hospital, Whitham Road, Sheffield S102SJ, UK
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  • Author Footnotes
    q Tel.: +1 717 531 5960; fax: +1 717 531 8796.
    Allan Lipton
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    q Tel.: +1 717 531 5960; fax: +1 717 531 8796.
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    Department of Medicine and Oncology, Penn State University, College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, H046, P.O. Box 850, Hershey, PA 17033-0850, United States
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    r Tel.: +1 412 688 6571; fax: +1 412 688 6960.
    G. David Roodman
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    r Tel.: +1 412 688 6571; fax: +1 412 688 6960.
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    Department of Medicine, VA Pittsburgh Healthcare System, R&D 151-U, Rm 2E-113, University Drive, Pittsburgh, PA 15240, United States
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    s Tel.: +1 317 278 6014; fax: +1 978 246 8044.
    Theresa A. Guise
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    s Tel.: +1 317 278 6014; fax: +1 978 246 8044.
    Affiliations
    Department of Internal Medicine, Division of Endocrinology, Indiana University, 541 N. Clinical Dr., P.O. Box 801419, Indianapolis, IN 46202-5111, United States
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    t Tel.: +1 585 275 5837; fax: +1 585 276 2047.
    Brendon F. Boyce
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    t Tel.: +1 585 275 5837; fax: +1 585 276 2047.
    Affiliations
    Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Anatomic Pathology, 601 Elmwood Ave, Box 626, Rochester, NY 14642, United States
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    u Tel.: +1 412 641 6500; fax: +1 412 641 2296.
    Adam M. Brufsky
    Footnotes
    u Tel.: +1 412 641 6500; fax: +1 412 641 2296.
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    Department of Medicine, UPMC Cancer Center, Magee-Womens Hospital, 300 Halket Street, Suite 4628, Pittsburgh, PA 15123, United States
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    v Tel.: +33 1 478 785 737; fax: +33 1 478 778 772.
    Philippe Clézardin
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    v Tel.: +33 1 478 785 737; fax: +33 1 478 778 772.
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    INSERM Research Unit U664, Faculté de Médecine Laennec, Rue Guillaume Paradin, 69372 Lyon cedex 08, France
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    w Tel.: +44 (0) 114 271 2414; fax: +44 (0) 114 271 1711.
    Peter I. Croucher
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    University of Sheffield Medical School, Department of Human Metabolism, Room DU34, D Floor, Beech Hill Road, Sheffield S10 2RX, United Kingdom
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    x Tel.: +1 206 288 7222; fax: +1 206 288 1025.
    Julie R. Gralow
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    Department of Medical Oncology, University of Washington, Seattle Cancer Care Alliance, 825 Eastlake Ave E, G3-630, Seattle, WA 98109-1023, United States
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    y Tel.: +49 6421 286 6486; fax: +49 6421 286 7070.
    Peyman Hadji
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    y Tel.: +49 6421 286 6486; fax: +49 6421 286 7070.
    Affiliations
    Department of Endocrinology, Reproductive Medicine and Osteoporosis, University Hospital of Giessen, Marburg, Germany

    Marburg GmbH, Marburg, Germany

    Department of Gynecology, Baldingerstrasse, D-35033 Marburg, Germany
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    z Tel.: +44 (0) 114 271 3854; fax: +44 (0) 114 271 1711.
    Ingunn Holen
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    Academic Unit of Oncology, University of Sheffield Medical School, Academic Unit of Clinical Oncology, DU39, Beech Hill Road, Sheffield S10 2RX, United Kingdom
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    Gregory R. Mundy
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    Department of Medicine, Vanderbilt University Medical Center, 1235 Medical Research Building IV, 2215B Garland Avenue, Nashville, TN 37232-0575, United States
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    Matthew R. Smith
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    Department of Genitourinary Medical Oncology, Massachusetts General Hospital Cancer Center, 55 Fruit St, Yawkey 7038, Boston, MA 02114, United States
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    Larry J. Suva
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    Medical Sciences, Department of Orthopaedic Surgery, Center for Orthopaedic Research University of Arkansas for Medical Sciences, 4301 West Markham Street, Mail 644, Little Rock, AR 72205, United States
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  • Author Footnotes
    q Tel.: +1 717 531 5960; fax: +1 717 531 8796.
    r Tel.: +1 412 688 6571; fax: +1 412 688 6960.
    s Tel.: +1 317 278 6014; fax: +1 978 246 8044.
    t Tel.: +1 585 275 5837; fax: +1 585 276 2047.
    u Tel.: +1 412 641 6500; fax: +1 412 641 2296.
    v Tel.: +33 1 478 785 737; fax: +33 1 478 778 772.
    w Tel.: +44 (0) 114 271 2414; fax: +44 (0) 114 271 1711.
    x Tel.: +1 206 288 7222; fax: +1 206 288 1025.
    y Tel.: +49 6421 286 6486; fax: +49 6421 286 7070.
    z Tel.: +44 (0) 114 271 3854; fax: +44 (0) 114 271 1711.
    aa Tel.: +1 615 322 6110; fax: +1 615 343 2611.
    ab Tel.: +1 617 724 5257; fax: +1 617 726 4899.
    ac Tel.: +1 501 526 6110; fax: +1 501 686 8987.

      Abstract

      Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy.

      Keywords

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