Elimination of aggressive cancers by a ferroptosis-inducing PROTAC

Identifying molecular pathways and compounds that target these pathways is critical for improving patient outcomes. RNF4, an E3-ubiquitin ligase, is pivotal in oncoprotein stabilization and DNA repair, enhancing cancer cell survival driving tumorigenesis.

Elevated RNF4 levels are associated with worse prognosis in cancer patients. Here, we describe the development of R4VPs, protein-targeted chimeras (PROTACs) that promote RNF4 degradation, and reduce the levels of its stabilized oncoproteins. Notably, R4VPs induce ferroptotic cell death selectively in cancer cells, sparing non-tumorigenic and primary cells.