Letai Anthony G
Dana-Farber Cancer Institute, Harvard Medical School, Dana 530B, 44 Binney Street, Boston, Massachusetts 02052, USA.
Nat Rev Cancer. 2008 Feb;8(2):121-32. doi: 10.1038/nrc2297.
Cancer cells survive despite violating rules of normal cellular behaviour that ordinarily provoke apoptosis. The blocks in apoptosis that keep cancer cells alive are therefore attractive candidates for targeted therapies. Recent studies have significantly increased our understanding of how interactions among proteins in the BCL2 family determine cell survival or death. It is now possible to systematically determine how individual cancers escape apoptosis. Such a determination can help predict not only whether cells are likely to be killed by antagonism of BCL2, but also whether they are likely to be sensitive to chemotherapy that kills by the intrinsic apoptotic pathway.
癌细胞尽管违反了通常会引发细胞凋亡的正常细胞行为规则,却依然能够存活。因此,阻止细胞凋亡从而使癌细胞存活的机制成为了靶向治疗的理想靶点。最近的研究显著增进了我们对于BCL2家族中蛋白质之间的相互作用如何决定细胞存活或死亡的理解。现在已经能够系统地确定单个癌症是如何逃避细胞凋亡的。这样的确定不仅有助于预测细胞是否可能因BCL2拮抗剂而被杀死,还能预测它们是否可能对通过内源性凋亡途径杀死细胞的化疗敏感。