Longevity & AgingNew PROTAC Drug Degrades Cancer's Immortality Enzyme TERT
Telomerase reverse transcriptase (TERT) drives cancer immortality and therapy resistance through both its enzymatic activity and non-catalytic protein interactions. Researchers at Northwestern and University of Chicago designed NU-PRO-1, a covalent PROTAC linking the TERT-targeting inhibitor NU-1 to a VHL E3-ligase ligand, enabling proteasomal degradation of TERT rather than mere inhibition. In MCF7 breast cancer cells, NU-PRO-1 induced transient but significant TERT degradation within hours via the ubiquitin-proteasome pathway. Crucially, at degrading doses, NU-PRO-1 outperformed NU-1 alone in prolonging DNA damage after radiation, suggesting TERT's non-catalytic functions meaningfully contribute to cancer's DNA repair capacity—a gap conventional inhibitors cannot fully address.
