Apoptosis regulation

Apoptosis regulation is a complex biological system of signaling pathways that controls programmed cell death, a vital mechanism for tissue homeostasis and the elimination of damaged or potentially harmful cells (Nature Reviews Molecular Cell Biology, 2017). This regulation involves a balance between pro-apoptotic proteins, such as BAX and BAK, and anti-apoptotic proteins, such as BCL-2 and MCL-1, which determine the integrity of the mitochondrial membrane and the subsequent activation of executioner caspases (Cell Death & Differentiation, 2005). In cancer, cells often develop mechanisms to evade apoptosis, such as the overexpression of survival proteins, which is recognized as a fundamental hallmark of malignancy (Cell, 2011). Conversely, excessive apoptosis is a primary driver of pathology in neurodegenerative and cardiovascular diseases. Drug development in this field focuses on shifting the balance toward cell death in tumors using small molecules like Venetoclax to inhibit BCL-2 or death receptor agonists to trigger extrinsic pathways (Frontiers in Oncology, 2021).

Other names

Programmed cell death regulationApoptotic signaling pathwayRegulation of apoptotic processCell death signaling

Therapeutic agents targeting the apoptosis regulation machinery primarily act as BH3 mimetics that inhibit anti-apoptotic BCL-2 family proteins, SMAC mimetics that antagonize Inhibitors of Apoptosis Proteins (IAPs) to release caspases, or agonists of death receptors (e.g., TRAIL-R1/2) to initiate the extrinsic death pathway (Nature Reviews Drug Discovery, 2005; Frontiers in Oncology, 2021).