Centenera Margaret M, Fitzpatrick Alyssa K, Tilley Wayne D, Butler Lisa M
Adelaide Prostate Cancer Research Centre, University of Adelaide, Adelaide, Australia.
Biochim Biophys Acta. 2013 Apr;1835(2):211-8. doi: 10.1016/j.bbcan.2012.12.005. Epub 2012 Dec 31.
Heat shock protein 90 (Hsp90) is a molecular chaperone that regulates the maturation, activation and stability of critical signaling proteins that drive the development and progression of prostate cancer, including the androgen receptor. Despite robust preclinical data demonstrating anti-tumor activity of first-generation Hsp90 inhibitors in prostate cancer, poor clinical responses initially cast doubt over the clinical utility of this class of agent. Recent advances in compound design and development, use of novel preclinical models and further biological insights into Hsp90 structure and function have now stimulated a resurgence in enthusiasm for these drugs as a therapeutic option. This review highlights how the development of new-generation Hsp90 inhibitors with improved physical and pharmacological properties is unfolding, and discusses the potential contexts for their use either as single agents or in combination, for men with metastatic prostate cancer.
热休克蛋白90（Hsp90）是一种分子伴侣，可调节驱动前列腺癌发生和发展的关键信号蛋白的成熟、激活和稳定性，这些蛋白包括雄激素受体。尽管有强有力的临床前数据表明第一代Hsp90抑制剂在前列腺癌中具有抗肿瘤活性，但最初较差的临床反应让人对这类药物的临床实用性产生怀疑。化合物设计与开发方面的最新进展、新型临床前模型的应用以及对Hsp90结构和功能的进一步生物学见解，如今激发了人们对将这些药物作为一种治疗选择的热情再度高涨。本综述重点介绍了具有改善的物理和药理特性的新一代Hsp90抑制剂的研发进展，并讨论了它们作为单一药物或联合用药用于转移性前列腺癌男性患者的潜在适用情况。
