SelfProDeg: Generation of selective and efficient protein degraders for the treatment of glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive and prevalent brain tumor, responsible for 4% of cancer-related deaths. Current therapies—surgery, radiotherapy, and chemotherapy—only extend life expectancy to 15–20 months due to frequent tumor recurrence.

The project aims to overcome these barriers by developing innovative antibodies that enable tissue-selective degradation of proteins critical to GBM progression and can effectively penetrate brain tissue. A central objective is the creation of the first screening platform to identify new lysosome-targeting receptors (LTRs), which are essential for directing extracellular and membrane-associated proteins to degradation pathways. By expanding the repertoire of LTRs and improving their efficiency and selectivity, the project seeks to address limitations of current targeted protein degradation strategies such as PROTACs and LYTACs.

To further increase therapeutic precision, the project will integrate novel conditional activation mechanisms into antibody-based degraders. This approach will allow antibodies to remain inactive in healthy tissues and only become activated within diseased environments, reducing dose-limiting side effects. Ultimately, the research will deliver both selective degraders for glioblastoma treatment and a pioneering discovery platform to identify new protein-degrading receptors, offering broad opportunities for developing safer and more effective therapies for GBM and other diseases. This research is funded by the 2025 Postdoctoral Junior Leader fellowships Retaining Call from F. La Caixa