Combination therapy using LHRH and somatostatin analogues plus dexamethasone in androgen ablation refractory prostate cancer patients with bone involvement: a bench to bedside approach.

The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.