# STK11 / KEAP1 co-mutations

Source: https://onco.cc/terms/stk11-keap1/  
OnCo record `stk11-keap1` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: STK11; KEAP1; co-mutation; co-mutations; co-mutated; STK11/KEAP1; LKB1; SMARCA4

## Notes

- What the pairing is worth, with the qualification that is usually dropped. STK11 is mutated in 13 to 18% of lung adenocarcinomas and KEAP1 in 11 to 18%, rising to 22.1% each in cohorts selected for checkpoint blockade (cBioPortal). STK11 loss produces an immune-poor tumour with low PD-L1 (Skoulidis 2015, 2018); KEAP1 loss was the only independent predictor of short survival among 330 KRAS-mutant patients (hazard ratio 1.96, and 3.54 from the start of immunotherapy) (Arbour 2018). The qualification: across 1,261 patients, both effects were confined to KRAS-mutant tumours, with no effect in KRAS wild-type disease (Ricciuti 2022), and in the randomised pembrolizumab trials neither gene changed the treatment benefit at all (Mok 2023, Garassino 2023). So it is prognostic information to be read alongside KRAS status, not a reason to withhold immunotherapy.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/STK11
- Wikipedia: https://en.wikipedia.org/wiki/STK11

## Connected records

- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [KRAS mutation subtypes (G12C, G12D, G12V)](https://onco.cc/terms/kras-mutation-subtypes/), [PD-L1 expression testing (22C3, SP142, SP263)](https://onco.cc/terms/pd-l1-testing/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [KEAP1](https://onco.cc/targets/keap1/), [KRAS](https://onco.cc/targets/kras/), [STK11](https://onco.cc/targets/stk11/)
- key papers: [Associations of tissue tumour mutational burden and mutational status with clinical outcomes in KEYNOTE-042](https://onco.cc/key-papers/paper-keynote-042-tmb-mutations-ann-oncol-2023/), [Associations of tissue tumour mutational burden and mutational status with clinical outcomes with pembrolizumab plus chemotherapy versus chemotherapy for metastatic non-small-cell lung cancer](https://onco.cc/key-papers/paper-keynote-189-407-tmb-jtocrr-2023/), [Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities](https://onco.cc/key-papers/paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015/), [Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status](https://onco.cc/key-papers/paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022/), [Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer](https://onco.cc/key-papers/paper-arbour-kras-co-mutation-outcomes-ccr-2018/), [Molecular determinants of response to anti-PD-1 and anti-PD-L1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing](https://onco.cc/key-papers/paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018/), [Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies](https://onco.cc/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/), [STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma](https://onco.cc/key-papers/paper-kras-nsclc-cancer-discov-2018/), [The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer](https://onco.cc/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/)
- biomarkers: [STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma](https://onco.cc/biomarkers/stk11-keap1-loss/)

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