title: Zoledronic acid: an unending tale for an antiresorptive agent.
abstract: BACKGROUND
  Therapy with zoledronic acid (ZOL) is a standard for patients with malignant bone disease. However, the antitumor effects of ZOL are demonstrated only in the preclinical setting and, therefore, they require pharmacological and molecular optimization. ZOL blocks protein isoprenylation, a pleiotropic and basic biochemical process within the cells regulating the activity of several proteins involved in survival and proliferating pathways.
  
  
  METHODS
  The present review will cover different areas of research from pharmacology to cell biology and molecular biology regarding both direct and indirect anticancer effects of ZOL in humans. The challenge in demonstrating the clinical activity of ZOL is mainly based on its pharmacokinetic properties, which are discussed in detail.
  
  
  RESULTS
  New data about the modes to overcome the limitations of ZOL and the following therapeutic strategies to implement its anticancer activity are described: i) development of pharmacological combinations; ii) finding of new molecular targets of ZOL; and iii) development of new pharmacological formulations of ZOL.
  
  
  CONCLUSIONS
  In conclusion, ZOL has still underestimated anticancer properties that require further investigation in both preclinical and clinical settings.
authors.affiliation: II University of Naples, Department of Biochemistry and Biophysics, Via S. M. Costantinopoli 16, 80138 Naples, Italy. michele.caraglia@unina2.it
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Monica
authors.initials: M
authors.lastname: Marra
authors.forename: Silvio
authors.initials: S
authors.lastname: Naviglio
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Addeo
authors.forename: Alberto
authors.initials: A
authors.lastname: Abbruzzese
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D006878:Hydroxides / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D010087:Oxides / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D017368:Protein Prenylation / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D006878:Hydroxides; D007093:Imidazoles; D010087:Oxides; D000077211:Zoledronic Acid