Labi V, Erlacher M, Kiessling S, Villunger A
Division of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Austria.
Cell Death Differ. 2006 Aug;13(8):1325-38. doi: 10.1038/sj.cdd.4401940. Epub 2006 Apr 28.
Induction of apoptosis in tumour cells, either by direct activation of the death receptor pathway using agonistic antibodies or recombinant ligands, or direct triggering of the Bcl-2-regulated intrinsic apoptosis pathway by small molecule drugs, carries high hopes to overcome the shortcomings of current anticancer therapies. The latter therapy concept builds on a more detailed understanding of how Bcl-2-like molecules maintain mitochondrial integrity and how BH3-only proteins and Bax/Bak-like molecules can undermine it. Means to unleash the apoptotic potential of BH3-only proteins in tumour cells, or bypass the need for BH3-only proteins by blocking possible interactions of Bcl-2-like prosurvival molecules with Bax and/or Bak allowing their direct activation, constitute interesting options for the design of novel anticancer therapies.
通过使用激动性抗体或重组配体直接激活死亡受体途径，或通过小分子药物直接触发Bcl-2调节的内源性凋亡途径来诱导肿瘤细胞凋亡，为克服当前抗癌疗法的缺点带来了很高的期望。后一种治疗理念基于对Bcl-2样分子如何维持线粒体完整性以及仅含BH3结构域的蛋白和Bax/Bak样分子如何破坏这种完整性的更详细理解。释放肿瘤细胞中仅含BH3结构域的蛋白的凋亡潜力，或通过阻断Bcl-2样促生存分子与Bax和/或Bak的可能相互作用以允许它们直接激活，从而绕过对仅含BH3结构域的蛋白的需求，这些方法为新型抗癌疗法的设计提供了有趣的选择。
