Marzo Isabel, Naval Javier
Departamento de Bioquimica y Biologia Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Pedro Cerbuna, 12, 50009 Zaragoza, Spain.
Biochem Pharmacol. 2008 Oct 15;76(8):939-46. doi: 10.1016/j.bcp.2008.06.009. Epub 2008 Jun 28.
Escape from apoptosis is often a hallmark of cancer cells, and is associated to chemotherapy resistance or tumor relapse. Proteins from the Bcl-2 family are the key regulators of the intrinsic pathway of apoptosis, controlling the point-of no-return and setting the threshold to engage the death machinery in response to a chemical damage. Therefore, Bcl-2 proteins have emerged as an attractive target to develop novel anticancer drugs. Current pharmacological approaches are focused on the use of peptides, small inhibitory molecules or antisense oligonucleotides to neutralize antiapoptotic Bcl-2 proteins, lowering the threshold and facilitating apoptosis of cancer cells. We discuss here recent advances in the development of Bcl-2 targeted anticancer therapies.
逃避细胞凋亡通常是癌细胞的一个标志，并且与化疗耐药性或肿瘤复发相关。Bcl-2家族蛋白是细胞凋亡内在途径的关键调节因子，控制着细胞凋亡的不可逆转点，并设定了启动死亡机制以应对化学损伤的阈值。因此，Bcl-2蛋白已成为开发新型抗癌药物的一个有吸引力的靶点。目前的药理学方法主要集中在使用肽、小分子抑制剂或反义寡核苷酸来中和抗凋亡的Bcl-2蛋白，降低阈值并促进癌细胞的凋亡。我们在此讨论Bcl-2靶向抗癌疗法开发的最新进展。
