Category: cell_death
Programmed cell death. Intrinsic (mitochondrial) pathway: pro-apoptotic BH3-only proteins (BIM, BID, PUMA, NOXA) activate effector BAX/BAK → MOMP (mitochondrial outer membrane permeabilization) → cytochrome c release → apoptosome (Apaf-1 + caspase-9) → executioner caspase-3/7. Antagonized by anti-apoptotic Bcl-2 family (BCL-2, BCL-xL, MCL-1, BCL-w). Extrinsic (death receptor): Fas/TNF/TRAIL → DISC → caspase-8 → caspase-3/7 + BID truncation (crosstalk to mitochondria). VENETOCLAX is a BH3-mimetic that selectively occupies Bcl-2's BH3 groove → frees pro-apoptotic effectors → triggers apoptosis in Bcl-2-dependent cancer cells (CLL, AML). Navitoclax adds BCL-xL inhibition (causes thrombocytopenia — platelets depend on BCL-xL).