The anti-tumor potential of zoledronic acid.
Bone is a favorable microenvironment for tumor cell colonization because of abundant growth factors released during active bone resorption. Bisphosphonates can dramatically affect the ability of tumor cells to grow in bone by inhibiting osteoclast-mediated bone resorption and by depriving tumors of growth-promoting signals. Moreover, bisphosphonates have direct anti-tumor effects in vitro via induction of apoptosis. Zoledronic acid is a nitrogen-containing bisphosphonate that has demonstrated potent anti-tumor activity in vitro and in vivo. In vitro studies have provided important clues as to the molecular mechanisms by which zoledronic acid induces apoptosis of human breast cancer cell lines. Studies in multiple myeloma and breast cancer models have shed further light on the possible mechanisms underlying the in vivo anti-tumor effects of zoledronic acid. These studies have led to the development of novel strategies to target specific molecular pathways involved in osteoclast maturation and activity, tumor cell metastasis, and tumor growth and survival. The clinical application of these strategies may ultimately prevent bone metastasis.
Croucher
P
P
Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford, UK. peter.croucher@orthopaedic-surgery.oxford.ac.uk
Jagdev
S
S
Coleman
R
R
D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D001862:Bone Resorption / Q000517:prevention & control*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D002986:Clinical Trials as Topic; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid