Cancer cell apoptosis

Cancer cell apoptosis is the process by which malignant cells undergo programmed cell death, either via the intrinsic (mitochondrial) or extrinsic (death receptor-mediated) pathways. The intrinsic pathway involves the balance of pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane permeabilization, cytochrome c release, and caspase activation. The extrinsic pathway is triggered at the cell surface by TNF-family ligands binding their receptors (e.g., TRAIL binding DR4/DR5), leading to recruitment of adaptor proteins and caspase-8 activation. Many cancers evade apoptosis by upregulating anti-apoptotic proteins, mutating p53, or suppressing death receptor signaling. Therapeutic strategies focus on restoring apoptotic responses by targeting these molecular mechanisms, with drugs including Bcl-2 inhibitors (e.g., Venetoclax), death receptor agonists (e.g., recombinant TRAIL or DR4/DR5 antibodies), HDAC inhibitors, and others[1][2][4][5][6][7][8][9]. The complexity and redundancy of these pathways pose significant therapeutic challenges, such as resistance and toxicity. Biomarker-driven approaches (e.g., Bcl-2/Mcl-1 abundance, caspase activity, p53 status) are employed to select patients for therapies exploiting apoptosis in cancer.

Other names

Cancer apoptosisInduction of cancer cell deathTumor cell apoptosis

Activation of the intrinsic (mitochondrial) apoptosis pathway: targeting pro- and anti-apoptotic Bcl-2 family proteins (e.g., cocktails of Bcl-2/Bcl-xL inhibitors induce cytochrome c release and downstream caspase activation); Activation of the extrinsic (death receptor) pathway: stimulation of TNF-family death receptors (e.g., via TRAIL analogs and DR4/DR5 agonists); Inhibition of anti-apoptotic proteins (e.g., Bcl-2, Bcl-xL, Mcl-1); Promotion of pro-apoptotic factors (e.g., Bax, Bak, PUMA, NOXA, Bid); Activation of initiator (caspase-8, -9) and executioner caspases (caspase-3, -7); Epigenetic modulation (e.g., HDAC inhibitors upregulate apoptotic genes)