Senescent cell anti-apoptotic pathway (SCAP)

Senescent cell anti-apoptotic pathways (SCAPs) are networks of signaling and regulatory molecules that allow senescent cells to resist programmed cell death (apoptosis) despite the accumulation of internal damage and external pro-apoptotic signals[2][6][1]. Key components of SCAPs include BCL-2 family proteins, PI3K/AKT pathway, p53/p21/serpine signaling, tyrosine kinase pathways, and others, which collectively help senescent cells survive in normally toxic environments[2][1][4]. SCAPs are considered critical therapeutic targets because their inhibition—by "senolytic" drugs—selectively eliminates senescent cells, which are implicated in aging, cancer, fibrosis, and other chronic diseases[4][2][6]. Drugs targeting SCAPs (e.g., dasatinib, quercetin, navitoclax, fisetin, FOXO4-DRI) act by disrupting specific pro-survival mechanisms, thereby restoring apoptosis in senescent cells while ideally sparing healthy cells[2][4][6]. Monitoring biomarkers such as SA-β-galactosidase, p16^INK4a^, and BCL-2 family protein levels may help identify patients most likely to benefit from SCAP-targeting therapies. Key challenges in targeting SCAPs include off-target effects, risk of unintended tissue damage, and the need for precise patient selection[4][1][6].

Other names

Senescent cell antiapoptotic pathwaySenescent cell anti-apoptotic pathwaysSCAPAnti-apoptotic pathways in senescent cells

Inhibition of BCL-2 family proteins (e.g., BCL-2, BCL-X_L_, BCL-W); Inhibition of PI3K/AKT pathway; Disruption of FOXO4-p53 interaction; Inhibition of tyrosine kinases; Targeting p53/p21/serpine pathway