title: Targeting the Bone Microenvironment in Metastatic Castration-Resistant Prostate Cancer.
abstract: Metastatic castration-resistant prostate cancer (mCRPC) is universally incurable and represents an area of substantial unmet medical need. Novel targets and therapeutic strategies have emerged based on an improved understanding of the crosstalk between prostate cancer cells and the bone microenvironment. A wide variety of signaling systems including the RANKL/RANK/OPG, IGF-I, FGF and Wnt:DKK-1 pathways can be targeted to suppress tumor growth and treatment resistance. Antisurvival factor therapy can increase the efficacy of standard antineoplastic regimens by targeting biologic molecules acting as "survival factors" within the bone microenvironment. Novel agents can also be used to mobilize the host immune system to attack prostate cancer cells. Clinical testing of these therapeutic approaches has produced encouraging objective clinical responses in subsets of patients with mCRPC. The present review summarizes data regarding the emerging strategies used to target the bone microenvironment in mCRPC.
authors.affiliation: Albert Einstein College of Medicine Jacobi Medical Center, Suite 3N1 1400 Pelham Pkwy S. Bronx, NY 10461. msaouel@gmail.com.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Msaouel
authors.forename: Jose Nahun
authors.initials: JN
authors.lastname: Galeas
authors.forename: Alejandro Recio
authors.initials: AR
authors.lastname: Boiles
authors.forename: Ramiro Rancier
authors.initials: RR
authors.lastname: Ruiz
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002470:Cell Survival / Q000187:drug effects; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents