title: Bisphosphonates for cancer treatment: Mechanisms of action and lessons from clinical trials.
abstract: A growing body of evidence points toward an important anti-cancer effect of bisphosphonates, a group of inexpensive, safe, potent, and long-term stable pharmacologicals that are widely used as osteoporosis drugs. To date, they are already used in the prevention of complications of bone metastases. Because the bisphosphonates can also reduce mortality in among other multiple myeloma, breast, and prostate cancer patients, they are now thoroughly studied in oncology. In particular, the more potent nitrogen-containing bisphosphonates have the potential to improve prognosis. The first part of this review will elaborate on the direct and indirect anti-tumoral effects of bisphosphonates, including induction of tumor cell apoptosis, inhibition of tumor cell adhesion and invasion, anti-angiogenesis, synergism with anti-neoplastic drugs, and enhancement of immune surveillance (e.g., through activation of γδ T cells and targeting macrophages). In the second part, we shed light on the current clinical position of bisphosphonates in the treatment of hematological and solid malignancies, as well as on ongoing and completed clinical trials investigating the therapeutic effect of bisphosphonates in cancer. Based on these recent data, the role of bisphosphonates is expected to further expand in the near future outside the field of osteoporosis and to open up new avenues in the treatment of malignancies.
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium. Electronic address: Heleen.VanAcker@uantwerp.be.
authors.forename: Heleen H
authors.initials: HH
authors.lastname: Van Acker
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Anguille
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Willemen
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research (CORE), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Evelien L
authors.initials: EL
authors.lastname: Smits
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
authors.forename: Viggo F
authors.initials: VF
authors.lastname: Van Tendeloo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002986:Clinical Trials as Topic; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates
keywords: Bisphosphonates; Cancer immunology; Clinical trials; Direct anti-cancer effects; Hematological malignancies; Solid tumors