The Vontz Center for Molecular Studies, University of Cincinnati, OH 45267-0508, United States.
Cancer Lett. 2012 Dec 28;325(2):147-54. doi: 10.1016/j.canlet.2012.06.016. Epub 2012 Jul 7.
Targeting the ubiquitin+proteasome protein degradation pathway with the therapeutic agent bortezomib has significantly improved the survival of cancer patients but drug resistance inevitably develops. Aggresomes and the autophagy pathway serve as compensatory protein-clearance mechanisms that eradicate potentially toxic proteins to promote resistance to proteasome inhibitors and, hence, tumor survival. Pre-clinical evidence has emerged to demonstrate active crosstalk between these protein degradation pathways and has revealed novel therapeutic targets and strategies. Translational research and clinical trials are now focused on these pathways to prevent the emergence of drug resistance, enhance apoptosis and further improve the survival of cancer patients.
使用治疗药物硼替佐米靶向泛素蛋白酶体蛋白降解途径显著改善了癌症患者的生存，但不可避免地会产生耐药性。聚集物和自噬途径作为补偿性蛋白清除机制，可消除潜在的毒性蛋白，从而促进对蛋白酶体抑制剂的耐药性，并促进肿瘤的生存。临床前证据表明，这些蛋白降解途径之间存在着积极的相互作用，并揭示了新的治疗靶点和策略。转化研究和临床试验目前都集中在这些途径上，以防止耐药性的出现，增强细胞凋亡，并进一步提高癌症患者的生存率。
