Caspase-dependent apoptotic signaling pathway

The caspase-dependent apoptotic signaling pathway is a fundamental biological process responsible for programmed cell death, characterized by the sequential activation of cysteine-aspartic proteases known as caspases (Source: NIH/NCBI). This pathway is divided into the intrinsic (mitochondrial) and extrinsic (death receptor) routes, both of which converge on executioner caspases like Caspase-3 to dismantle the cell (Source: StatPearls). In oncology, tumor cells often evade this pathway by upregulating anti-apoptotic proteins such as BCL-2 or downregulating pro-apoptotic factors, leading to uncontrolled growth and resistance to chemotherapy (Source: PubMed). Targeting this pathway involves the use of small molecules like BH3 mimetics (e.g., Venetoclax) that inhibit BCL-2, thereby lowering the threshold for caspase activation (Source: PubChem). Other therapeutic approaches include IAP (Inhibitor of Apoptosis Protein) antagonists and death receptor agonists designed to re-engage the apoptotic machinery in malignant cells (Source: Wikipedia). Monitoring the efficacy of such treatments often involves measuring biomarkers like cleaved Caspase-3 or PARP cleavage (Source: PubMed). However, systemic activation of this pathway can lead to significant safety concerns, including hepatotoxicity and lymphopenia, due to off-target effects on healthy tissues (Source: NIH). Note: This entry describes a biological pathway rather than a single molecular target.

Other names

Caspase cascadeProgrammed cell death pathwayIntrinsic apoptotic pathwayExtrinsic apoptotic pathwayCaspase-dependent apoptotic signaling pathway in tumor cells

Activation of a proteolytic cascade involving initiator and executioner caspases to induce programmed cell death.