title: Could targeting bone delay cancer progression? Potential mechanisms of action of bisphosphonates.
abstract: Although dissemination may occur early in the course of many cancers, the development of overt metastases depends upon a variety of factors inherent to the cancer cells and the tissue(s) they colonize. The time lag between initial dissemination and established metastases could be several years, during which period the bone marrow may provide an unwitting sanctuary for disseminated tumor cells (DTCs). Survival in a dormant state within the bone marrow may help DTCs weather the effects of anticancer therapies and seed posttreatment relapses. The importance of the bone marrow for facilitating DTC survival may vary depending on the type of cancer and mechanisms of tumor cell dissemination. By altering the bone microenvironment, bisphosphonates may reduce DTC viability. Moreover, some bisphosphonates have demonstrated multiple anticancer activities. These multiple mechanisms may help explain the improvement in disease outcomes with the use of zoledronic acid in malignancies like breast cancer and multiple myeloma.
authors.affiliation: Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. aftr@wustl.edu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Aft
authors.forename: Jose-Ricardo
authors.initials: JR
authors.lastname: Perez
authors.forename: Noopur
authors.initials: N
authors.lastname: Raje
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates