Apoptosis signaling pathways in tumor cells

Apoptosis pathways in tumor cells comprise two main molecular cascades—the extrinsic (death receptor-mediated) and intrinsic (mitochondrial-mediated) apoptotic pathways. The extrinsic pathway is activated by death ligands such as TRAIL, TNFα, and FasL binding to their corresponding receptors (DR4/DR5, TNFR1, Fas), initiating a cascade involving caspase-8 and adaptor proteins (e.g., FADD). The intrinsic pathway is regulated by the Bcl-2 family, which controls mitochondrial membrane permeabilization resulting in cytochrome c release, apoptosome formation, and activation of caspase-9. Both converge on executioner caspases (e.g., caspase-3), leading to cell death. Dysregulation or resistance of these pathways is a hallmark of cancer, promoting tumor growth and drug resistance. Drugs that modulate apoptosis pathways are an important class of anti-cancer agents, but targeting these pathways can pose safety risks due to potential cytotoxicity to normal tissues

Other names

Apoptosis pathwaysapoptotic pathwaysapoptotic signaling cascades

Activation of death receptors (extrinsic pathway); Inhibition of Bcl-2 family anti-apoptotic proteins (intrinsic pathway); Release of cytochrome c and caspase activation.