Attack the backup copy when a tumour has lost the original gene
Tumours often lose one of a pair of near-identical genes. They then depend entirely on the remaining copy, which a drug can block, killing only the cancer.
SMARCA4-mutant cancers depend on SMARCA2; MTAP-deleted cancers depend on PRMT5 in a methylthioadenosine-dependent manner; other paralog pairs (for example ARID1A/ARID1B, ENO1/ENO2) show the same logic. Paralog dependencies are the most systematic way to exploit tumour-suppressor loss, which is otherwise undruggable. Selective SMARCA2 degraders and MTA-cooperative PRMT5 inhibitors have reached the clinic.
- The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.
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not linked directly; found by shared links- PersonFrancisca Vazquez
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