Moreover, in a tour de force involving simultaneous mutation of the genes for eight BH3-only proteins, five anti-apoptotic Bcl-2 family proteins, as well as Bax and Bak in HCT116 colorectal carcinoma cells, O'Neill et al. showed that Bax or Bak are able to associate with the outer mitochondrial membrane, activate, and cause apoptosis spontaneously, without being activated by any BH3-only protein [25]. This evidence concerns the gene BAK1 and colorectal carcinoma.