Endothelin and Skeletal Metastases in Hormone-Refractory Prostate Cancer

摘要: Abstract Skeletal metastases represent a major complication of advanced hormone-refractory prostate cancer (HRPC). These lesions affect around 85% patients and provide poor quality life due to associated pathological fractures, spinal compression pain. Metastatic HRPC is incurable typically fatal within 2 years diagnosis. At present, there no effective treatment for delaying disease progression. Current options based on chemotherapy, radiotherapy bisphosphonates are essentially palliative do not appear prolong survival. HRPC, therefore, represents considerable unmet clinical need, new therapies required alter the course process beyond providing palliation. Many factors involved in bone remodelling, substantial body evidence suggests role endothelin-1 (ET-1) pathophysiology metastatic HRPC. In binding ET-1 specific receptor (ET A ) only enhances osteoblastic activity promotes development lesions, but also generates mitogenic anti-apoptotic milieu. vivo vitro studies show that ET-1-stimulated growth inhibited when blocked. Highly potent ET -receptor antagonists, an exciting management potentially therapeutic target delay or prevention skeletal