摘要：Many cancer cells, including B-cell and lung cancers, display elevated expression of anti-apoptotic Bcl-2 proteins as a survival strategy to cope with oncogenic stress [1]. In cancer cells, Bcl-2 is loaded with pro- apoptotic BH3-only proteins, thereby not only preventing Bax/Bak activation but also rendering them "primed to death" at the mitochondria. The last decade, different compounds have been developed to antagonize this anti-apoptotic function of Bcl-2 at the mitochondria [1]. The most promising molecules are the BH3 mimetics (like ABT-737 and ABT-263), which release Bim from the hydrophobic cleft of Bcl-2 (or Bcl-XL) formed by the BH3-BH1-BH2 domains resulting in Bax/Bak-mediated apoptosis in cancer but not in healthy cells (Fig. 1). The last generation BH3 mimetics (ABT-199) spares platelets by avoiding Bcl-XL inhibition [1].
