Ashkenazi Avi
Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080-4918, USA.
Nat Rev Drug Discov. 2008 Dec;7(12):1001-12. doi: 10.1038/nrd2637. Epub 2008 Nov 7.
Each day, the human body eliminates billions of unwanted cells by apoptotic suicide. Apoptosis provides an important barrier against cancer; however, specific mutations enable some tumour cells to escape apoptotic death and become more malignant. Two signalling pathways initiate apoptosis: one acts through intracellular Bcl-2 proteins, the other through cell-surface pro-apoptotic receptors. New molecular insights have inspired the development of pro-apoptotic receptor agonists (PARAs), including the recombinant human protein apoptosis ligand 2/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) and agonistic monoclonal antibodies to its signalling receptors. Acting alone, or in concert with other agents, PARAs may overcome key apoptosis blocks and direct cancer cells to self-destruct.
每天，人体通过凋亡性自杀清除数十亿个不需要的细胞。凋亡是抵御癌症的重要屏障；然而，特定的突变使一些肿瘤细胞能够逃避凋亡死亡并变得更具恶性。有两条信号通路启动凋亡：一条通过细胞内Bcl-2蛋白起作用，另一条通过细胞表面促凋亡受体起作用。新的分子见解推动了促凋亡受体激动剂（PARA）的开发，包括重组人蛋白凋亡配体2/肿瘤坏死因子相关凋亡诱导配体（Apo2L/TRAIL）及其信号受体的激动性单克隆抗体。PARA单独作用或与其他药物协同作用，可能克服关键的凋亡障碍并引导癌细胞自我毁灭。
