Group trials by broken mechanism, not by organ or single mutation
Rare cancers often share a broken cellular machine even when they arise in different organs. Grouping patients by that shared fault makes trials possible.
Tumour-agnostic approvals so far follow single alterations such as NTRK fusions or mismatch repair deficiency. Many rare cancers instead share mechanism classes — SWI/SNF complex loss including SMARCB1 and SMARCA4, chromatin regulator loss, fusion-driven transcription factor addiction, metabolic enzyme mutations — that could define baskets with dozens of contributing diagnoses and a common therapeutic hypothesis such as EZH2 or PRMT5 dependence.
- 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.
- Tumour heterogeneity and clonal evolution · A tumour is many tumours. Treatments that kill most cells leave the rest to grow back, changed.
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.
Pages like this
not linked directly; found by shared links- IdeaTurn chromosomal chaos into a weakness with KIF18A inhibitors
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Shares PRMT5/MAT2A synthetic lethality for MTAP-deleted mesothelioma, Synthetic lethality, Synthetic lethality approaches, CRISPR functional genomics.
- IdeaWRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers
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- IdeaDegraders for the fusion proteins that drive childhood sarcomas
Shares Gene fusion, CRISPR functional genomics, Rare and paediatric cancers without markets, Sarcomas (soft tissue, bone, GIST).
- IdeaA standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling
Shares Gene fusion, Tumour-agnostic (tissue-agnostic) approval, Rare and paediatric cancers without markets, Trial design, endpoints and cost.
- Key paperDefining a Cancer Dependency Map: which genes each cancer cell line cannot live without
Shares DepMap (Cancer Dependency Map), Synthetic lethality, Synthetic lethality approaches, CRISPR functional genomics.
- PersonChristopher R. Vakoc
Shares Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET), CRISPR functional genomics, Sarcomas (soft tissue, bone, GIST).
- InstitutionThe Wistar Institute
Shares EZH2, Synthetic lethality, Ovarian cancer.