Apoptosis

Apoptosis is the first-discovered and best-characterized form of regulated cell death, executed through caspase enzyme cascades. It proceeds via two routes: the intrinsic (mitochondrial) pathway, triggered by BAX/BAK-mediated mitochondrial outer membrane permeabilization, and the extrinsic pathway, triggered by death receptors at the cell surface. Morphologically, apoptotic cells shrink, condense their chromatin, and are rapidly cleared by phagocytes (efferocytosis) without normally provoking inflammation. Because overexpression of anti-apoptotic proteins such as BCL-2 can drive tumor formation, evasion of apoptosis was one of the original “hallmarks of cancer,” and it remains the only regulated cell death pathway for which drugs (e.g., the BCL-2 inhibitor venetoclax) have reached approved clinical use, most notably in chronic lymphocytic leukemia.