TNF and cancer: It can be concluded that in cancer cells exposed to HDACIs, pro-apoptotic genes involved in the intrinsic (BAK, BAX, and APAF1) and/or extrinsic (FAS, FAS-L, TRAIL, DR5, and TNF-α) apoptotic pathways are up-regulated, while anti-apoptotic genes (XIAP, Bcl-2) are downregulated (43).