Targeting the endothelin axis in prostate carcinoma.
Prostate cancer is the most common malignancy in men in Western countries. Until the last decade, the main available therapeutic options were based on hormonal therapy. For castration-refractory prostate carcinoma, from 2004, the combination of chemotherapy with docetaxel and prednisone has shown to improve survival in this subset of patients. Many agents have been tested either alone or in combination with this standard therapy, trying to find synergistic effects between drugs, and to target specific pathways that influence tumor growth, invasiveness, angiogenesis, and the development of distant metastasis. Endothelin antagonists have been recently studied, as they can get involved in many of these oncogenic pathways, and results are encouraging; nevertheless, the right setting to use them, whether to use them in monotherapy or in combination with other agents, and if they really improve the survival of our patients, are questions that remain to be addressed. In this review, we summarize the role of endothelins in tumoral biology and specifically in prostate carcinoma natural history, and the results obtained in the clinical trials involving this new therapeutic group.
Medical Oncology Department, Translational Oncology Unit, University Hospital La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain. alvaropintomarin@gmail.com
Alvaro
A
Pinto
María
M
Merino
Pilar
P
Zamora
Andrés
A
Redondo
Beatriz
B
Castelo
Enrique
E
Espinosa
D000077868:Atrasentan; D001842:Bone and Bones / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism*; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011759:Pyrrolidines / Q000627:therapeutic use
D016232:Endothelins; D011759:Pyrrolidines; C511404:ZD4054; D000077868:Atrasentan