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Direct and indirect anticancer activity of bisphosphonates: a brief review of published literature

Michael Gnant1, Philippe Clézardin

  • 1Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. michael.gnant@meduniwien.ac.at

Cancer Treatment Reviews
|October 11, 2011
PubMed

Insights

Bisphosphonates, used to treat bone disease, show promise in preventing cancer recurrence by altering the bone marrow microenvironment. These agents exhibit direct and indirect anticancer effects, impacting both tumor cells and their surroundings.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • The bone marrow microenvironment facilitates cancer cell evasion of therapy, contributing to disease persistence and relapse.
  • Dormant micrometastases are implicated in cancer recurrence, but the distinction between cancer stem cells and those with limited metastatic potential remains unclear.
  • Bisphosphonates are established treatments for malignant bone disease and bone loss associated with cancer therapy.

Purpose of the Study:

  • To review preclinical and clinical studies on bisphosphonates' anticancer activities.
  • To explore how bisphosphonates modify the bone marrow microenvironment to inhibit cancer cell survival.
  • To summarize the direct and indirect anticancer effects of bisphosphonates on tumor cells and their microenvironment.

Main Methods:

  • Literature review of preclinical and early clinical studies.
  • Analysis of bisphosphonate mechanisms of action.
  • Examination of clinical outcomes in various cancer types.

Main Results:

  • Bisphosphonates demonstrate direct and indirect anticancer activities.
  • Zoledronic acid improved survival in adjuvant breast cancer, multiple myeloma, and other advanced cancers.
  • Antiresorptive therapy delayed bone metastases in prostate cancer.

Conclusions:

  • Altering the bone marrow microenvironment is a key strategy to prevent cancer recurrence.
  • Bisphosphonates offer potential anticancer benefits by targeting both tumor cells and their microenvironment.
  • Further research is ongoing to elucidate the full anticancer potential of bisphosphonates and related agents.

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