Cory Suzanne, Adams Jerry M
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Cancer Cell. 2005 Jul;8(1):5-6. doi: 10.1016/j.ccr.2005.06.012.
Impairment of apoptosis, the physiologic cell death process, is central to cancer development and renders tumors refractory to cytotoxic therapy. Bcl-2, the oncoprotein activated in follicular lymphoma, inhibits the conserved cell death pathway triggered by diverse cytotoxic agents, as do several close relatives. A small-molecule antagonist of these proteins has now been designed by Oltersdorf et al. Strikingly, ABT-737 sensitizes many tumors to cytotoxic agents and is effective as a single agent against certain lymphomas and solid tumors, provoking stable regression in some tumor xenografts. Hence, this work validates Bcl-2-like proteins as important new targets in cancer therapy.
细胞凋亡作为一种生理性细胞死亡过程，其功能受损是癌症发展的核心问题，并且会使肿瘤对细胞毒性疗法产生耐药性。Bcl-2是在滤泡性淋巴瘤中被激活的一种癌蛋白，它能抑制由多种细胞毒性药物触发的保守性细胞死亡途径，其几个近亲蛋白也有同样作用。Oltersdorf等人现已设计出一种针对这些蛋白的小分子拮抗剂。引人注目的是，ABT-737能使许多肿瘤对细胞毒性药物敏感，并且作为单一药物对某些淋巴瘤和实体瘤有效，在一些肿瘤异种移植模型中能引起稳定的肿瘤消退。因此，这项研究证实了Bcl-2样蛋白是癌症治疗中重要的新靶点。
