Degraders for the fusion proteins that drive childhood sarcomas
Some sarcomas in children are caused by two genes fused into one abnormal protein. That protein is the whole disease, but no drug binds it. Destroying it instead of blocking it could work.
EWS-FLI1 in Ewing sarcoma and PAX3-FOXO1 in alveolar rhabdomyosarcoma are single, tumour-specific, genetically validated drivers with no enzymatic activity. Degradation via recruited E3 ligases, or indirect destabilisation through their obligate cofactors (for example BRD9 in the ncBAF complex for synovial sarcoma, already showing clinical activity with BRD9 degraders), offers a route. Their absence from normal tissue means an unusually wide therapeutic index.
- The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.
- Rare and paediatric cancers without markets · Taken together rare cancers are a fifth of all cancers, but each one alone is too small for a company to invest in.
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not linked directly; found by shared links- IdeaMolecular glues that break the MYC-MAX partnership
Shares C4 Therapeutics, PROTACs & molecular glues (targeted protein degradation), The undruggable drivers.
- IdeaScreen glue-like compounds against every cancer cell line and publish it
Shares C4 Therapeutics, PROTACs & molecular glues (targeted protein degradation), The undruggable drivers.
- IdeaDesign protein degraders small enough to get into the brain
Shares C4 Therapeutics, PROTACs & molecular glues (targeted protein degradation), The undruggable drivers.
- IdeaThe pathology lab triggers a trial referral the day a rare cancer is diagnosed
Shares Gene fusion, Rare and paediatric cancers without markets, Sarcomas (soft tissue, bone, GIST).
- IdeaAttack the backup copy when a tumour has lost the original gene
Shares CRISPR functional genomics, PROTACs & molecular glues (targeted protein degradation), The undruggable drivers.
- IdeaA synthetic lethality map for every cancer driver in every tissue context
Shares Patient-derived xenografts, CRISPR functional genomics, The undruggable drivers.
- IdeaAn open organoid bank for cancers too rare to have models
Shares Patient-derived xenografts, Rare and paediatric cancers without markets, Sarcomas (soft tissue, bone, GIST).
- InstitutionThe Jackson Laboratory Cancer Center
Shares Patient-derived xenografts, CRISPR functional genomics.