title: Bone microenvironment-targeted manipulations for the treatment of osteoblastic metastasis in castration-resistant prostate cancer.
abstract: BACKGROUND
  Most patients with advanced prostate cancer will develop incurable bone metastasis. Although prostate cancer is the quintessential androgen-dependent neoplastic disease in males, the tumor will ultimately become refractory to androgen ablation treatment. Understanding the complex dialog between prostate cancer and the bone microenvironment has allowed the development of promising treatment strategies.
  
  
  METHODS
  The present review summarizes the pathophysiology of prostate cancer bone metastasis and provides a concise update on bone microenvironment-targeted therapies for prostate cancer. The current and future prospects and challenges of these strategies are also discussed.
  
  
  CONCLUSIONS
  A wide variety of signaling pathways, bone turnover homeostatic mechanisms and immunoregulatory networks are potential targets for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Anti-survival factor therapy can enhance the efficacy of existing treatment regimens for mCRPC by exploiting the interaction between the bone microenvironment and androgen signaling networks. In addition, many novel bone microenvironment-targeted strategies have produced promising objective clinical responses. Further elucidation of the complex interactions between prostate cancer cells and the bone stroma will open up new avenues for treatment interventions that can produce sustained cancer suppression.
authors.affiliation: Jacobi Medical Center, Department of Internal Medicine, Albert Einstein College of Medicine , Bronx, NY , USA.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Msaouel
authors.forename: Gayathri
authors.initials: G
authors.lastname: Nandikolla
authors.forename: Spyros G
authors.initials: SG
authors.lastname: Pneumaticos
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D002369:Castration; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents