drug-resistance
A senolytic is an agent that selectively kills senescent cells, rather than merely suppressing their secretory output. Senescent cells survive partly by leaning on anti-apoptotic proteins, so inhibitors of BCL-2 and BCL-xL such as ABT-263 (navitoclax) and ABT-737 act as senolytics, as does the combination of dasatinib and quercetin.
Other approaches target proteins displayed on the surface of senescent cells, including CAR-T cells directed against such markers. ABT-263 has been evaluated clinically in advanced solid tumors, including in combination with gemcitabine, where thrombocytopenia is its characteristic dose-limiting toxicity.
Related terms
Source papers
- Chemotherapy-induced senescence promotes stroma stiffness and antioxidant adaptation to promote chemoresistance in pancreatic ductal adenocarcinoma doi:10.1038/s41467-026-75772-5