12 Mechanisms of bone metastasis in prostate cancer: clinical implications Pavlos Msaouel MD Research Fellow Nikos Pissimissis PhD Student Antonios Halapas MD, PhD Research Fellow Michael Koutsilieris * MD, PhD Professor and Chairman Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Micras Asias St, Goudi-Athens 11527, Greece Prostate cancer shows a strong predilection to spread to the bones. Once prostate tumour cells are engrafted in the skeleton, curative therapy is no longer possible and palliative treatment be- comes the only option. Herein, we review the multifactorial mechanisms and complex cellular interactions that take place inside the bone metastatic microenvironment. Emphasis is given to the detection and treatment of the micrometastatic stage of prostate cancer, as well as our re- cent attempts to target the bone metastasis microenvironment-related survival factors using an anti-survival factor manipulation which can increase the efficacy of anticancer therapies such as androgen ablation therapy and chemotherapy in advanced prostate cancer. Key words: bone metastasis; cancer therapy; micrometastasis; prostate cancer; survival factors. Prostate cancer tends to invade the pelvic lymph nodes and spread to distant organs, mainly via the blood stream, showing a strong predilection for bones. 1–4 Almost all pa- tients with advanced prostate cancer show histological skeletal involvement. 5,6 The median time between the diagnosis of a clinically evident metastasis in bones and death * Corresponding author. Tel.: þ30 2107462597; Fax: þ30 2107462571. E-mail address: mkoutsil@med.uoa.gr (M. Koutsilieris). 1521-690X/$ - see front matter ª 2008 Published by Elsevier Ltd. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 22, No. 2, pp. 341–355, 2008 doi:10.1016/j.beem.2008.01.011 available online at http://www.sciencedirect.com