Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Treat Rev. 2008;34 Suppl 1:S19-24. doi: 10.1016/j.ctrv.2008.03.006. Epub 2008 May 16.

Antitumor effects of bisphosphonates: promising preclinical evidence.

Author information

1
Division of Endocrinology, Department of Medicine, University of Virginia, Aurbach Medical Research Building, PO Box 801419, Charlottesville, VA 22903, United States. tag4n@virginia.edu

Abstract

The majority of patients with advanced cancer will ultimately develop bone metastases. The bone microenvironment provides fertile soil for a cycle of tumor growth and bone destruction that increases the risk of debilitating and potentially life-limiting skeletal-related events. Therefore, developing appropriate strategies to prevent bone metastases is critical. Bisphosphonates used to treat and prevent skeletal-related events resulting from multiple myeloma and bone metastases secondary to solid tumors, may also have direct and indirect antitumor effects. Emerging evidence from in vitro and in vivo preclinical studies in several tumor types suggests that bisphosphonates can reduce tumor burden in bone and soft tissue, inhibit angiogenesis, prevent tumor cell invasion and adhesion in bone, and induce tumor cell apoptosis. The powerful antiresorptive properties of bisphosphonates appear to directly prevent tumor cell growth and angiogenesis; in addition, combining bisphosphonates with cytotoxic chemotherapy may provide further antitumor synergies. Sequential application of cytotoxic chemotherapy (e.g., doxorubicin, paclitaxel, and gemcitabine) followed by bisphosphonates has been shown to induce significantly more tumor cell apoptosis than either agent alone in vitro and effectively inhibits tumor growth in vivo. Furthermore, in vivo data suggest that optimizing the dosing schedule may significantly increase survival. Overall, preclinical data suggesting that bisphosphonates have antitumor potential are promising and have provided the impetus for several ongoing clinical studies.

PMID:
18486348
DOI:
10.1016/j.ctrv.2008.03.006
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center