Pro-apoptotic genes

Pro-apoptotic genes encode a diverse group of proteins that collectively facilitate programmed cell death (apoptosis) in response to internal or external stress signals (Jan & Chaudhry, 2019). This category includes the Bcl-2 family members such as BAX, BAK, and BH3-only proteins (e.g., BIM, PUMA, NOXA), as well as the caspase family of proteases and the tumor suppressor TP53 (Aubrey et al., 2018; Singh et al., 2019). These genes play a critical role in maintaining tissue homeostasis and eliminating damaged or potentially cancerous cells (Singh et al., 2019). In many malignancies, the function of pro-apoptotic genes is compromised through mutations, epigenetic silencing, or the upregulation of anti-apoptotic survival proteins like BCL-2 and BCL-XL (Kalkavan & Green, 2018). Pharmacological strategies to exploit these pathways include BH3 mimetics, such as venetoclax, which inhibit anti-apoptotic proteins to effectively prime the cell for death by releasing sequestered pro-apoptotic factors (Souers et al., 2013). Additionally, therapies targeting the p53 pathway or direct caspase activators are being explored to bypass resistance mechanisms in various cancers (Aubrey et al., 2018; Kalkavan & Green, 2018).

Other names

Death-promoting genesPro-apoptotic factorsApoptosis-inducing genesBH3-only genes

Drugs targeting this pathway primarily function by either inhibiting anti-apoptotic proteins (e.g., BCL-2, BCL-XL) to release sequestered pro-apoptotic proteins like BAX and BAK, or by restoring the activity of pro-apoptotic transcription factors like p53 to induce the expression of death-promoting genes (Jan & Chaudhry, 2019; Souers et al., 2013).