STK11 / KEAP1 co-mutations
Two genes whose loss, often alongside a KRAS mutation, makes lung cancer 'cold' to immunotherapy and shortens survival on standard treatment. They are the reason two KRAS-mutant lung cancers can behave completely differently.
STK11 (LKB1) and KEAP1 are inactivated in about 15-20% of lung adenocarcinomas each. Tumours with these losses have low PD-L1, few infiltrating T cells and poor responses to PD-1 blockade and chemo-immunotherapy, and KEAP1 loss also blunts chemotherapy and radiotherapy through antioxidant (NRF2) activation. They are stratification factors and exclusion criteria in modern lung trials, and are targets of dedicated strategies: glutaminase inhibition for KEAP1, and adding CTLA-4 blockade (POSEIDON subgroup) for STK11. SMARCA4 loss is a third co-mutation with similar prognostic weight.
Pages like this
not linked directly; found by shared links- IdeaTurn a brake back on: drugs that reactivate the PP2A phosphatase
Shares KRAS, Non-small-cell lung cancer.
- TrialCodeBreaK 200
Shares KRAS, Non-small-cell lung cancer.
- TrialKRYSTAL-12
Shares KRAS, Non-small-cell lung cancer.
- PersonMiriam Merad
- TermImmuno-oncology (IO) and checkpoint blockade
Shares PD-L1 expression testing (22C3, SP142, SP263), Hot vs cold tumours.
- IdeaBlock the complement signal that recruits tumour-protecting cells
- TrialKrascendo 1
Shares KRAS, Non-small-cell lung cancer.
- ProductOlomorasib
Shares KRAS, Non-small-cell lung cancer.