In vitro and in vivo antitumor effects of bisphosphonates

Philippe Clézardin, Pierrick Fournier, Sandrine Boissier, Olivier Peyruchaud

Research output: Contribution to journalReview article

75 Scopus citations

Abstract

Bisphosphonates are powerful inhibitors of osteoclast-mediated bone resorption. They are currently used in the palliative treatment of bone metastases. However, bisphosphonates do not only act on osteoclasts. There is now extensive in vitro preclinical evidence that bisphosphonates can act on tumor cells: they inhibit tumor cell adhesion to mineralized bone as well as tumor cell invasion and proliferation. Bisphosphonates induce also tumor cell apoptosis and stimulate γδ T cell cytotoxicity against tumor cells. In vivo, bisphosphonates inhibit bone metastasis formation and reduce skeletal tumor burden. This may reflect direct antitumor effects and indirect effects via inhibition of bone resorption. In addition, bisphosphonates inhibit experimental angiogenesis in vitro and in vivo. Understanding the molecular mechanisms through which bisphosphonates act on tumor and endothelial cells will be undoubtedly an important task in the future. It will allow the design of clinical trials to investigate whether the antitumor activity of bisphosphonates can be realized in the clinical setting.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalCurrent Medicinal Chemistry
Volume10
Issue number2
DOIs
StatePublished - Jan 1 2003

Keywords

  • Adhesion
  • Angiogenesis
  • Apoptosis
  • Bisphosphonate
  • Bone
  • Invasion
  • Metastasis
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Clézardin, P., Fournier, P., Boissier, S., & Peyruchaud, O. (2003). In vitro and in vivo antitumor effects of bisphosphonates. Current Medicinal Chemistry, 10(2), 173-180. https://doi.org/10.2174/0929867033368529