Improving the outcome of patients with castration-resistant prostate cancer through rational drug development.
Improving the outcome of patients with castration-resistant prostate cancer through rational drug development.
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DOI：
10.1038/sj.bjc.6603223
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发表时间：
2006-10-09
影响因子：
8.8
通讯作者：
de Bono, J S
中科院分区：
文献类型：
--
作者：
Attard, G;Sarker, D;Reid, A;Molife, R;Parker, C;de Bono, J S
去势抵抗性前列腺癌（CRPC）现在是男性癌症相关死亡的第二大常见原因。尽管多西他赛最近在两项大型随机III期研究中显示可延长CRPC患者的生存期，但这些患者的后续治疗选择仍然有限。对去势抵抗的分子原因有了更深入的了解，就可以更合理地开发新药，许多新药现在正在临床开发中。治疗靶点包括肾上腺类固醇合成途径、雄激素受体信号传导、表皮生长因子受体家族、胰岛素生长因子-1受体、组蛋白脱乙酰酶、热休克蛋白90和肿瘤血管系统。针对这些靶点的药物使人们深入了解这种疾病的分子发病机制，并有望提高患者的生活质量和生存率。最后，最近发现的染色体易位导致至少3个ETS基因（ERG，ETV 1，ETV 4）之一的上调，可能会导致新的药物治疗这种疾病。
Castration-resistant prostate cancer (CRPC) is now the second most common cause of male cancer-related mortality. Although docetaxel has recently been shown to extend the survival of patients with CRPC in two large randomised phase III studies, subsequent treatment options remain limited for these patients. A greater understanding of the molecular causes of castration resistance is allowing a more rational approach to the development of new drugs and many new agents are now in clinical development. Therapeutic targets include the adrenal steroid synthesis pathway, androgen receptor signalling, the epidermal growth factor receptor family, insulin growth factor-1 receptor, histone deacetylase, heat shock protein 90 and the tumour vasculature. Drugs against these targets are giving an insight into the molecular pathogenesis of this disease and promise to improve patient quality of life and survival. Finally, the recent discovery of chromosomal translocations resulting in the upregulation of one of at least 3 ETS genes (ERG, ETV1, ETV4) may lead to novel agents for the treatment of this disease.