Gleave Martin, Chi Kim N
Division of Urology, University of British Columbia, The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia V5Z 3J5, Canada.
Ann N Y Acad Sci. 2005 Nov;1058:1-15. doi: 10.1196/annals.1359.001.
Discovery and targeting of genes mediating treatment resistance may lead to development of novel therapies that delay progression of recurrent and refractory cancers. Clusterin is a stress-associated cytoprotective chaperone expressed in many cancers that is upregulated in an adaptive cell survival manner by various apoptotic triggers and confers treatment resistance. Here, we review clusterin's functional role in regulating treatment-induced apoptosis and the use of a second generation antisense oligonucleotide to inhibit clusterin expression to enhance the cytotoxic effects of hormone- and chemotherapy in prostate and other xenograft models, as well as in recent human trials.
发现介导治疗抗性的基因并将其作为靶点，可能会促使新型疗法的研发，从而延缓复发性和难治性癌症的进展。簇集素是一种与应激相关的细胞保护伴侣蛋白，在许多癌症中都有表达，它通过各种凋亡触发因素以适应性细胞存活的方式上调，并赋予治疗抗性。在此，我们综述了簇集素在调节治疗诱导的细胞凋亡中的功能作用，以及在前列腺和其他异种移植模型中，以及最近的人体试验中，使用第二代反义寡核苷酸抑制簇集素表达以增强激素和化疗的细胞毒性作用。
