Proteolysis-Targeting Chimeras Induce Ferroptosis in Cancer: From Mechanism to Clinical Application - PubMed
6 hours ago
- #PROTAC
- #Ferroptosis
- #Cancer Therapy
- Ferroptosis is an iron-dependent cell death mechanism important for tumor suppression.
- Clinical application of ferroptosis is limited by regulatory complexity and lack of selective modulators.
- PROTACs offer a precise way to manipulate ferroptosis pathways.
- Key regulatory pathways include GPX4, FSP1, and DHODH.
- PROTAC design strategies focus on targeting these key nodes, with current efforts mainly on GPX4.
- Challenges include PROTAC druggability, ferroptosis's dual role, and compensatory resistance.
- Future strategies involve multi-target degraders, smart drug delivery, and combination therapies.
- Computational tools and AI are highlighted for accelerating PROTAC design.
- PROTAC technology has potential to treat refractory cancers by reactivating ferroptosis.