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lüll Prostate cancer cell survival pathways activated by bone metastasis microenvironment Tenta R; Sotiriou E; Pitulis N; Thyphronitis G; Koutsilieris MJ Musculoskelet Neuronal Interact 2005[Jun]; 5 (2): 135-44The development of resistance to anti-cancer therapies in bones is a major hurdle preventing long-lasting clinical responses to anti-cancer therapies in hormone refractory prostate cancer. Herein, we present the major signal transduction pathways, which are activated in prostate cancer cells residing at bone metastasis microenvironment. These intracellular signal transduction pathways can inhibit anti-cancer therapy-induced apoptosis of metastatic prostate cancer cells, thereby optimizing their survival, locally. Employment of this knowledge in a clinical setting provides the conceptual framework for the development of bone-targeted therapies for advanced prostate cancer. Indeed, bone metastasis microenvironment-targeted therapies illustrate a novel paradigm in cancer treatment: anti-tumor treatment strategies may not only aim at directly inducing cancer cell apoptosis, but can also target the tumor metastasis microenvironment, and neutralize the protection it confers on metastatic cancer cells.|Androgen Antagonists/therapeutic use[MESH]|Animals[MESH]|Antineoplastic Agents/therapeutic use[MESH]|Bone Neoplasms/blood/drug therapy/*secondary[MESH]|Cell Line, Tumor[MESH]|Cell Survival[MESH]|Drug Resistance, Neoplasm/*physiology[MESH]|Growth Substances/blood/metabolism[MESH]|Humans[MESH]|Male[MESH]|Neoplasm Metastasis/*pathology[MESH]|Prostatic Neoplasms/blood/drug therapy/*pathology[MESH]|Signal Transduction/*physiology[MESH] |