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Gene Symbol STK11
Synonyms hLKB1 | LKB1 | PJS
Gene Description STK11, serine/threonine kinase 11, is a tumor suppressor (PMID: 30562755) involved in cell metabolism, growth, polarity, and tumor suppression through the regulation of AMPK family members (PMID: 26398719). STK11 germline mutations are common in Peutz-Jeghers syndrome and somatic STK11 mutations have been identified in melanoma, lung, pancreatic, cervical, and endometrial cancers (PMID: 26877140, PMID: 29191602) and are often associated with resistance to immune checkpoint blockcade (PMID: 30626603).
ACMG Incidental List v2.0:
Yes, Peutz-Jeghers syndrome (PMID: 27854360)

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of SRC, ERBB2 (HER2), STK11, and NOTCH1 (PMID: 29636358). 29636358
STK11 D194E STK11 loss pancreatic cancer predicted - sensitive Everolimus Case Reports/Case Series Actionable In a clinical case study, a pancreatic cancer patient with Peutz-Jeghers syndrome harboring STK11 D194E and loss of heterozygosity of the other STK11 allele in the tumor achieved a partial response following treatment with Afinitor (everolimus), but progressed after 9 months (PMID: 21189378). 21189378
STK11 dec exp lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, knockdown of STK11 increased sensitivity to Mekinist (trametinib) in non-small cell lung cancer cell lines in culture and in xenograft models (PMID: 27821489). 27821489
STK11 Y253* STK11 dec exp stomach carcinoma predicted - sensitive Sirolimus Preclinical - Cell culture Actionable In a preclinical study, Rapamune (sirolimus) suppressed the growth of gastric carcinoma cells harboring STK11 Y253* with decreased Stk11 protein expression in culture (PMID: 32236518). 32236518
STK11 E199* lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 E199*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 E57fs lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 E57fs, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 F298L pituitary carcinoma predicted - sensitive Everolimus + Radiotherapy Case Reports/Case Series Actionable In a clinical case study, a patient with adenocorticotropic pituitary carcinoma harboring an STK11 inactivating mutation demonstrated clinical efficacy for greater than 6 months when treated with a combination of Afinitor (everolimus) and radiotherapy (PMID: 27615706). 27615706
STK11 F354L triple-receptor negative breast cancer predicted - sensitive Everolimus + Exemestane Case Reports/Case Series Actionable In a clinical case study, Afinitor (everolimus) in combination with Aromasin (exemestane) resulted in complete response ongoing for 14 months in a patient with metastatic triple-receptor negative breast cancer harboring STK11 F354L (PMID: 28550065). 28550065
STK11 inact mut endometrial cancer sensitive Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) reduced S6K phosphorylation and inhibited tumor growth in mouse models of STK11 (LKB1)-deficient endometrial cancer, including models with advanced tumors (PMID: 20142330). 20142330
STK11 inact mut Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 inactivating mutation and STK11 loss expression signature was associated with increased sensitivity to Selumetinib (AZD6244) in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 inact mut Advanced Solid Tumor sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 loss expression signature, which correlated to STK11 inactivating mutations, was associated with increased sensitivity to Mekinist (trametinib) in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 inact mut lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 inact mut Advanced Solid Tumor sensitive RDEA119 Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to RDEA119 in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 inact mut Advanced Solid Tumor sensitive CI-1040 Preclinical - Cell culture Actionable In a preclinical study, the presence an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to CI-1040 (PD184352) in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 inact mut Advanced Solid Tumor sensitive PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to PD-0325901 in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 K48fs lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 K48fs, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 loss Advanced Solid Tumor no benefit Metformin Preclinical - Cell culture Actionable In a preclinical study, Glucophage (metformin) was unable to inhibit cancer cell growth in cancer cell lines with biallelic loss of STK11 (PMID: 17062558, PMID: 18006825). 18006825 17062558
STK11 loss lung cancer resistant unspecified PD-1 antibody Preclinical Actionable In a preclinical study, PD-1 antibodies were ineffective in treating Stk11 (also known as Lkb1) deficient lung tumors in mice (PMID: 26833127). 26833127
STK11 loss lung non-small cell carcinoma no benefit Vistusertib Clinical Study - Cohort Actionable In a Phase II trial (NLMT), Vistusertib (AZD2014) treatment resulted in an observed objective response rate (ORR) of 0% (0/17), durable clinical benefit rate (DCBR) of 12% (2/17), and medial progression-free survival (PFS) of 2.3 months in patients with non-small cell lung cancer harboring STK11 loss, with Bayesian posterior probability for OR and DCBR of <0.01 and 0.06, respectively, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). 32669708
ERBB2 act mut STK11 loss breast cancer sensitive AZD8055 Preclinical Actionable In a preclinical study, AZD8055 inhibited tumor growth in a mouse model of spontaneous breast cancer harboring an ERBB2 (HER2) activating mutation and loss of STK11 (LKB1), which was enhanced by the addition of 2-DG (2-deoxyglucose) (PMID: 25436981). 25436981
STK11 mutant lung non-small cell carcinoma sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PF-05212384) inhibited growth of human non-small cell lung carcinoma cells harboring an STK11 mutation in culture (PMID: 21325073). 21325073
STK11 mutant lung non-small cell carcinoma decreased response unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, mutant STK11 correlated with a worse outcome with immune checkpoint inhibitor treatment compared to wild-type STK11 in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
STK11 mutant stomach cancer not applicable N/A Guideline Risk Factor Germline mutations in STK11 result in Peutz Jeghers syndrome, which is associated with increased risk of developing gastric cancer (NCCN.org). detail...
STK11 mutant pancreatic cancer not applicable N/A Guideline Risk Factor Germline mutations in STK11 result in Peutz Jeghers syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org). detail...
STK11 mutant lung non-small cell carcinoma decreased response unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, mutant STK11 correlated with a worse outcome with immune checkpoint inhibitor treatment compared to wild-type STK11 in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
STK11 mutant small intestine adenocarcinoma not applicable N/A Guideline Risk Factor Peutz-Jeghers syndrome often results from mutations in the STK11 gene, and is associated with increased risk of developing small bowel adenocarcinoma (NCCN.org). detail...
STK11 Q37* lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 Q37*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 W332* lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 W332*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 wild-type Advanced Solid Tumor sensitive Metformin Preclinical - Cell culture Actionable In a preclinical studies, Glucophage (metformin) inhibited cancer cell growth by activating the AMP kinase pathway in a variety of cancer cell lines that retained one functional allele of STK11 (PMID: 17062558, PMID: 18006825). 18006825 17062558