内皮素受体拮抗剂：原理、临床开发及在前列腺癌治疗中的作用。

Endothelin receptor antagonists: rationale, clinical development, and role in prostate cancer therapeutics.

作者信息

Thakkar Snehal G, Choueiri Toni K, Garcia Jorge A

机构信息

Department of Hematology and Medical Oncology, Taussig Cancer Center, The Cleveland Clinic Foundation, 9500 Euclid Avenue, R-35, Cleveland, OH 44195, USA.

出版信息

Curr Oncol Rep. 2006 Mar;8(2):108-13. doi: 10.1007/s11912-006-0045-1.

DOI:10.1007/s11912-006-0045-1

PMID:16507220

Abstract

The endothelins (ETs), which include ET-1, ET-2, ET-3, and their receptors ET-A and ET-B, play a major role in tumor growth, proliferation, apoptosis, angiogenesis, and bone metastasis. Atrasentan is a novel and selective inhibitor of ET-1 and ET-A. In vitro and in vivo data show that this oral agent is capable of inhibiting tumor cells in vitro. More recently, this agent was studied in several phase I trials with refractory carcinoma patients. Subsequently, phase II and III clinical trials evaluating atrasentan in patients with hormone-refractory prostate carcinoma have suggested that targeting this pathway may be a new therapeutic strategy in the treatment of solid malignancies, specifically, prostate cancer.

摘要

内皮素（ETs），包括ET-1、ET-2、ET-3及其受体ET-A和ET-B，在肿瘤生长、增殖、凋亡、血管生成和骨转移中起主要作用。阿曲生坦是一种新型的ET-1和ET-A选择性抑制剂。体外和体内数据表明，这种口服药物能够在体外抑制肿瘤细胞。最近，该药物在几项针对难治性癌症患者的I期试验中进行了研究。随后，在激素难治性前列腺癌患者中评估阿曲生坦的II期和III期临床试验表明，针对这一途径可能是治疗实体恶性肿瘤，特别是前列腺癌的一种新的治疗策略。