Castration-resistant Prostate Cancer: The Targeting of Bone Microenvironment-related Survival Factors For Prostate Cancer Cells

Background: Prostate cancer (PCa) patients shall develop eventually incurable bone metastasis. Although advanced prostate cancer is the best known example of androgen- dependent neoplasia, PCa patients after an excellent clinical response to adrogen ablation therapies (medical or surgical castration) will ultimately become castration resistant (CRPC). Methods: Analysis of cell-cell interactions within the sites of osteoblastic metastasis has revealed that survival factors (inhibitors of chemotherapy-induced apoptosis and androgen deprivation/medical or surgical castration-induced apopptosis) for prostate cancer cells are activated, locally. Results: The analysis of these cell-cell interactions between metastatic PCa cells and host tissue (bone) revealed that insulin-like growth factor I, transforming growth factor beta 1 (TGFβ1), interleukin 6 (IL-6) are the most important survival factors for prostate cancer cells residing in bones. Suppression of the bioavailability of such survival factors which can achieved by the administration of dexamethasone plus somatostatin analogues (anti-survival factor therapy: ASF therapy) was proven an effective hormonal manipulation for the treatment of CRPC. Conclusion: The present review provides an update on bone microenvironment cell-cell interactions forming the concept of the ASF therapy for CRPC.