title: The backbone of progress--preclinical studies and innovations with zoledronic acid.
abstract: Bisphosphonates (BPs) are antiresorptive agents that block pathologic bone resorption by inhibiting osteoclast function and later inducing osteoclast apoptosis. These agents localize to bone and break the vicious cycle of bone resorption that results from cross-stimulation between cancer cells and the bone remodeling cells, thereby reducing cancer-induced osteolysis and the tumor burden in bone. Thus nitrogen-containing BPs (N-BPs) have well established clinical benefits in the treatment of bone metastases from solid tumors and bone lesions from multiple myeloma. Preclinical data indicate that N-BPs, especially zoledronic acid (ZOL), can exert antimyeloma activity both in vitro and in vivo. Studies show that N-BPs can inhibit multiple intracellular processes essential for cancer cell proliferation and invasion and induce apoptosis. Furthermore, clinically relevant doses of N-BPs inhibit tumor-associated angiogenesis and can modulate macrophage phenotype in vivo, which is likely to contribute to anticancer effects.
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. jonathan.green@novartis.com
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Green
authors.forename: Andreas
authors.initials: A
authors.lastname: Guenther
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001862:Bone Resorption / Q000188:drug therapy* / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010010:Osteoclasts / Q000187:drug effects*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid