Molecular Profile Detail

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Profile Name STK11 inact mut
Gene Variant Detail

STK11 inact mut (loss of function)

Relevant Treatment Approaches mTOR Inhibitor mTORC1 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 Advanced Solid Tumor no benefit mTOR Inhibitor 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 non-small cell carcinoma no benefit mTOR Inhibitor 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 mTOR Inhibitor 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 D194E STK11 loss pancreatic cancer predicted - sensitive mTORC1 Inhibitor 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 mTORC1 Inhibitor 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 F298L pituitary carcinoma predicted - sensitive mTORC1 Inhibitor 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 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 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 lung adenocarcinoma not applicable N/A Clinical Study Emerging In clinical studies, STK11 mutations were associated with an inferior prognosis in patients with lung adenocarcinoma (PMID: 32312757, PMID: 32413741). 32413741 32312757
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 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 adenocarcinoma not predictive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring an STK11 mutation demonstrated a shorter progression free survival compared to patients with wild-type STK11 when treated with an unspecified PD-L1 antibody treatment, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
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 mutant lung non-squamous non-small cell carcinoma predicted - sensitive Camrelizumab + Rivoceranib Phase Ib/II Emerging In a Phase Ib/II trial, non-squamous NSCLC patients harboring STK11 and/or KEAP1 mutations (n=14) demonstrated an improved 12-month survival rate (85.1% vs 53.1%; p=0.01), and a trend towards improved objective response rate (42.9% vs 28.1%; p=0.33), disease control rate (92.9% vs 65.6%, p=0.053), and median progression-free survival (9.4 vs 5.3 months; p=0.64) compared to wild-type STK11/KEAP1 patients (n=32) treated with Camrelizumab (SHR-1210) plus Rivoceranib (apatinib) (PMID: 33323401; NCT03083041). 33323401
STK11 mutant lung adenocarcinoma not predictive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring an STK11 mutation demonstrated a shorter progression free survival compared to patients with wild-type STK11 when treated with an unspecified PD-1 antibody treatment, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
STK11 mutant lung non-small cell carcinoma sensitive mTOR Inhibitor 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 wild-type Advanced Solid Tumor sensitive mTOR Inhibitor 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
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 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 inact mut endometrial cancer sensitive mTORC1 Inhibitor 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 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 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 Advanced Solid Tumor sensitive Refametinib 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 Refametinib (BAY86-9766) 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 F354L triple-receptor negative breast cancer predicted - sensitive mTORC1 Inhibitor 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 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
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT04173507 Phase II Avelumab + Talazoparib Combination Treatment (Talazoparib Plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer With STK11 Gene Mutation (A LUNG-MAP Treatment Trial) Recruiting
NCT03375307 Phase II Olaparib Olaparib in Treating Patients With Metastatic or Advanced Urothelial Cancer With DNA-Repair Defects Recruiting