Potential Anticancer Properties of Bisphosphonates: Insights From Preclinical Studies

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Potential Anticancer Properties of Bisphosphonates: Insights From Preclinical Studies



Anti-Cancer Agents in Medicinal Chemistry, 12(2): 102-113.

Author(s): Philippe Clezardin.

Affiliation: Institut National de la Santeet de la Recherche Medicale, Research Unit UMR 1033, Facultede Medecine Lyon-Est (domaine Laennec), 8 Rue Guillaume Paradin, F-69372 Lyon,France.

Abstract

Bone is a common site of metastasis from advanced cancers, and metastasis to bone accounts for the majority of distant recurrences from breast and prostate cancers. Bone metastases are characterized by increased rates of bone turnover. Bisphosphonates are extensively used in the treatment of metastatic bone disease to reduce the rates of osteolysis and the risk of skeletal-related events. In addition, bisphosphonates have demonstrated direct and indirect anticancer potential in preclinical studies. These activities include induction of apoptosis, inhibition of invasion, synergistic cytotoxicity with chemotherapy agents, antiangiogenic properties, and modulation of immunologic activity against transformed cells. Notably, these activities of bisphosphonates are not limited to the bone microenvironment; indeed some effects are mediated on the cancer cells themselves. These preclinical data provide the rationale for the underlying potential clinical benefits from bisphosphonates (e.g., prevention of metastasis to bone and other sites in the early breast cancer setting and delayed disease progression in malignancies involving colonization of bone [e.g., multiple myeloma]). This review article summarizes the preclinical anticancer activities of bisphosphonates in various cancer types and evaluates their potential contributions to the recently demonstrated clinical effects.

Keywords:

Anticancer, Apoptosis, Bisphosphonates, Gamma-delta T cells, Synergy, Zoledronic acid, parathyroid hormone-related protein (PTHrP), guanosine triphosphatases (GTPases), myeloma-associated osteolysis.



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Article Details

Volume: 12
Issue Number: 2
First Page: 102
Last Page: 113
Page Count: 12
DOI: 10.2174/187152012799014977
Price: $58
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