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    BIOMARKER:

    STK11 mutation

    i
    Other names: Serine/Threonine-Protein Kinase 11, Liver Kinase B1, Serine/Threonine-Protein Kinase LKB1, Polarization-Related Protein LKB1, STK11, Serine/Threonine Kinase 11, Serine/Threonine-Protein Kinase STK11, Renal Carcinoma Antigen NY-REN-19
    Entrez ID:
    6794
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    5d
    Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome. (PubMed, World J Gastrointest Oncol)
    These two missense variants can be interpreted as likely pathogenic variants that mediated the onset of PJS in the two patients. These findings not only offer insights for clinical decision-making, but also serve as a foundation for further research and reanalysis of missense VUS in rare diseases.
    Journal
    |
    STK11 (Serine/threonine kinase 11)
    |
    STK11 mutation • AMPK expression
    6d
    Genomic and Transcriptomic Landscape of RET Wild-Type Medullary Thyroid Cancer and Potential Use of Mitogen-Activated Protein Kinase-Targeted Therapy. (PubMed, J Am Coll Surg)
    We identified molecular alterations and immune-related features that distinguish wtRET from mutRET MTC. While RET mutation drives MTC in the absence of other alterations, we showed that wtRET MTC frequently harbors MAPK pathway mutations. These findings may indicate a potential basis for MAPK-targeted therapy, possibly in combination with oncology immune-oncology agents for selected patients with wtRET MTC.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • STK11 (Serine/threonine kinase 11) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1)
    |
    PD-L1 expression • KRAS mutation • TMB-H • BRAF mutation • STK11 mutation • NF1 mutation • RET mutation • VHL mutation • HRAS mutation • RET wild-type
    |
    Retevmo (selpercatinib)
    8d
    Effect of the STK11 mutation on therapeutic efficacy and prognosis in patients with non-small cell lung cancer: a comprehensive study based on meta-analyses and bioinformatics analyses. (PubMed, BMC Cancer)
    Patients with STK11-mutant NSCLC had low PD-L1 expression and ORR to ICIs, and their PFS and OS were worse than patients with STK11wt after comprehensive treatment. In the future, more reasonable systematic treatments should be explored for this subgroup of patients with STK11-mutant NSCLC.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • STK11 (Serine/threonine kinase 11)
    |
    PD-L1 expression • STK11 mutation • PD-L1-L
    |
    5-fluorouracil • vinorelbine tartrate • Nutlin-3
    14d
    Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma. (PubMed, Oncoimmunology)
    The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.
    Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • CD8 (cluster of differentiation 8) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
    |
    EGFR mutation • STK11 mutation • KEAP1 mutation • SMARCA4 mutation • NFE2L2 mutation
    18d
    Proteogenomic Characterization Reveals Estrogen Signaling as a Target for Never-Smoker Lung Adenocarcinoma Patients without EGFR or ALK Alterations. (PubMed, Cancer Res)
    Collectively, this study enhanced our understanding of NENA NSLA by elucidating the proteogenomic landscape and proposed saracatinib as a potential treatment for this patient population that lacks effective targeted therapies. The proteogenomic landscape in never-smoker lung cancer without known driver mutations reveals prognostic proteins and enhanced estrogen signaling that can be targeted as a potential therapeutic strategy to improve patient outcomes.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • LLGL2 (LLGL Scribble Cell Polarity Complex Component 2) • ST14 (ST14 transmembrane serine protease matriptase)
    |
    STK11 mutation • ALK fusion • ROS1 fusion • SETD2 mutation
    |
    saracatinib (AZD0530)
    28d
    Lifileucel, an Autologous Tumor-infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors. (PubMed, Cancer Discov)
    In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. Two patients died of treatment-emergent adverse events: cardiac failure and multiple organ failure. Lifileucel is a potential treatment option for patients with mNSCLC refractory to prior therapy.
    Clinical • Journal • Checkpoint inhibition • Tumor mutational burden • Tumor-infiltrating lymphocyte • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11)
    |
    STK11 mutation • PD-L1 negative • TMB-L • PD-L1 negative + TMB-L
    |
    Amtagvi (lifileucel) • LN-145
    29d
    A Phase II Study of Sotorasib (AMG 510) in Participants with Previously Treated Stage IV or Recurrent KRASG12C Mutated Non-Squamous Non-Small Cell Lung Cancer (ECOG-ACRIN Lung-MAP Sub-Study) (SWOG-Spring 2024)
    There have been two treatment-related deaths, one due to cardiac arrest and one due to pneumonitis. Ten additional participants have experienced Grade 4 treatment-related adverse events, nine of which are non-hematologic toxicities.
    P2 data • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • TP53 wild-type • STK11 mutation • ALK fusion • KEAP1 mutation • ROS1 fusion • KRAS G12 • STK11 mutation + TP53 mutation
    |
    FoundationOne® CDx
    |
    Lumakras (sotorasib)
    1m
    Establishment and characterization of multiple patient-derived organoids from a case of advanced endometrial cancer. (PubMed, Hum Cell)
    Lastly, a drug screening identified four candidate reagents commonly effective to all PDOs. Collectively, we showed that multiple PDOs could help reproduce the spatial diversity of a tumor and serve as a valuable resource in UCS research in many respects.
    Journal • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CCNE1 (Cyclin E1)
    |
    TP53 mutation • KRAS mutation • HER-2 amplification • HER-2 mutation • HER-2 expression • STK11 mutation • CCNE1 amplification • CCNE1 mutation
    1m
    The frequency of NRAS mutation in stool samples of Iranian colorectal cancers compared to Finnish patients. (PubMed, J Res Med Sci)
    Mutations in NRAS and FGFR3 were observed only in the Iranian cohort, while APC mutations were exclusive for the Finnish cohort. Genes involved in MAPK and PI3K-MAPK pathways showed a higher frequency of mutations in Iranian patients which may have therapeutic implications.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • STK11 mutation • KIT mutation • APC mutation • AKT1 mutation
    2ms
    Roflumilast inhibits tumor growth and migration in STK11/LKB1 deficient pancreatic cancer. (PubMed, Cell Death Discov)
    PDE4 inhibitor Roflumilast inhibited STK11-KO cell migration and tumor size, further demonstrating that PDEs are essential for STK11-deficient cell migration. Our findings support the adoption of therapeutic strategies, including Roflumilast, for patients with STK11-mutated pancreatic cancer in order to improve treatment efficacy and ultimately prolong survival.
    Journal
    |
    STK11 (Serine/threonine kinase 11)
    |
    STK11 mutation
    2ms
    Clinicopathologic features, concurrent genomic alterations, and clinical outcomes of patients with KRAS G12D mutations in resected lung adenocarcinoma. (PubMed, Eur J Cancer)
    KRAS G12D-mutant lung adenocarcinoma harbored unique clinicopathologic and genomic characteristics. Despite not being prognostic in resected lung adenocarcinoma, KRAS G12D might be a valuable biomarker in combination with certain co-mutations for identifying relevant subgroups of patients that could eventually influence treatment regimens.
    Clinical data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • PD-L1 overexpression • KRAS G12D • STK11 mutation • KRAS G12 • TP53 expression
    2ms
    Genomic landscape of gynecologic cancers with poor prognosis in Japan, an analysis of the national database of comprehensive genomic profiling tests (AACR 2024)
    The C-CAT database offers insights into the mutational landscape of various cancers and histological subtypes, especially those with poor prognosis, highlighting the unmet needs for drug development in these gynecologic cancers.
    Tumor mutational burden • MSi-H Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A)
    |
    TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • ARID1A mutation • STK11 mutation • CDKN2A mutation
    |
    FoundationOne® CDx
    2ms
    Impact of KEAP1/STK11 co-mutations and NRF2 signaling on resistance to adagrasib in advanced NSCLC (AACR 2024)
    Background: KRAS G12C inhibitors (G12Ci) are revolutionizing the therapeutic landscape of advanced NSCLC, but mechanisms of limited clinical efficacy observed in some patients (pts) merit continued exploration. Co-mutations in KEAP1 and STK11 and NRF2 signaling define a subgroup of KG12C NSCLC pts with markedly distinct outcomes upon treatment with ada. The mTORi and ada combination shows high efficacy for targeting KG12C NSCLC harboring KEAP1 and STK11 co-mutations. The clinical safety and efficacy of mTORi nab-sirolimus and ada will be determined in the ongoing KRYSTAL-19 trial (NCT05840510).
    Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    KRAS mutation • STK11 mutation • KEAP1 mutation • NFE2L2 mutation • KEAP1 expression
    |
    HTG Transcriptome Panel
    |
    Krazati (adagrasib) • Fyarro (nanoparticle albumin-bound rapamycin)
    2ms
    Outcomes in patients treated with frontline immune checkpoint inhibition (ICI) for advanced NSCLC with KRAS mutations and STK11/KEAP1 comutations across PD-L1 levels. (PubMed, Lung Cancer)
    KRASm are associated with worse overall survival in PD-L1 negative NSCLC; however, this association is largely driven by comutations with STK11 and KEAP1, which are enriched in PD-L1 negative tumors.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    PD-L1 expression • KRAS mutation • STK11 mutation • PD-L1 negative • KRAS wild-type • KEAP1 mutation
    2ms
    STK11/LKB1 alterations worsen the poor prognosis of KRAS mutated early-stage non-squamous non-small cell lung carcinoma, results based on the phase 2 IFCT TASTE trial. (PubMed, Lung Cancer)
    This analysis reinforces KRAS mutations as predictive factors for relapse and poor survival in localized non-sq NSCLC. Furthermore, the presence of concomitant STK11/LKB1 mutations exacerbated the prognosis within the KRAS-mutated subset. These findings emphasize the clinical relevance of these molecular markers and their potential impact on treatment strategies in non-sq NSCLC.
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • ERCC1 (Excision repair cross-complementation group 1)
    |
    PD-L1 expression • KRAS mutation • EGFR mutation • STK11 mutation • ERCC1 expression
    |
    cisplatin • erlotinib • pemetrexed
    2ms
    Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer. (PubMed, Cancer Cell)
    KRASG12C inhibitors (adagrasib and sotorasib) have shown clinical promise in targeting KRASG12C-mutated lung cancers; however, most patients eventually develop resistance. Notably, expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • KRT6A (Keratin 6A)
    |
    KRAS mutation • KRAS G12D • STK11 mutation
    |
    Lumakras (sotorasib) • Krazati (adagrasib)
    2ms
    Sotorasib in KRAS G12C-mutated non-small cell lung cancer: A multicenter real-world experience from the compassionate use program in Germany. (PubMed, Eur J Cancer)
    First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.
    Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • STK11 mutation • KEAP1 mutation • KRAS G12 • KRAS G12C + PD-L1 expression
    |
    Lumakras (sotorasib)
    2ms
    Pancreas Registry and High Risk Registry (clinicaltrials.gov)
    P=N/A, N=1116, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2023 --> Nov 2033 | Trial primary completion date: Dec 2023 --> Nov 2033
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSH2 (MutS Homolog 2)
    |
    ATM mutation • STK11 mutation • PALB2 mutation • CDKN2A mutation
    3ms
    Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. (PubMed, Nat Med)
    A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.
    P2 data • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    STK11 (Serine/threonine kinase 11) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    STK11 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738) • oleclumab (MEDI9447) • danvatirsen (AZD9150)
    3ms
    Influence of TP53 Comutation on the Tumor Immune Microenvironment and Clinical Outcomes With Immune Checkpoint Inhibitors in STK11-Mutant Non-Small-Cell Lung Cancer. (PubMed, JCO Precis Oncol)
    STK11mut NSCLC with TP53 comutation is a distinct subgroup with an immunologically active TIME and metabolic reprogramming. These properties should be exploited to guide patient selection for novel ICI-based combination approaches.
    Clinical data • Journal • Checkpoint inhibition • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • STING (stimulator of interferon response cGAMP interactor 1)
    |
    TP53 mutation • TMB-H • MSI-H/dMMR • TP53 wild-type • STK11 mutation • MYC expression • HIF1A expression
    3ms
    Prevalence, clinical characteristics, and treatment outcomes of patients with KRAS-mutated non-squamous NSCLC and PD-L1 expression: Real-life data analysis (ELCC 2024)
    Analysis of progression-free survival (PFS) after the first line of treatment with immune checkpoint inhibitors (ICIs) in 30 pts with stage IV KRAS-mutated NSCLC and high PD-L1 showed a trend favoring patients presenting a co-mutation (mPFS 13.7mo KRAS co-mutated vs. 3.6mo in KRAS only; HR 0.26; CI 95% 0.09-0.070; p=0.19). Conclusions These findings emphasize the importance of further exploring PD-L1 role in KRAS mutated patients, especially by taking into account accompanying mutations in other genes evaluated by NGS.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • PTEN mutation • STK11 mutation • FGFR2 mutation • PD-L1 negative • KRAS wild-type • RAS wild-type • MET mutation • PIK3CA expression • KRAS expression
    |
    VENTANA PD-L1 (SP263) Assay
    3ms
    Cytopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumors in serous effusion (PubMed, Zhonghua Bing Li Xue Za Zhi)
    This tumor thus warrants careful consideration. Accurate diagnosis can greatly improve early diagnosis and treatment of these tumors.
    Journal • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • CD34 (CD34 molecule) • SALL4 (Spalt Like Transcription Factor 4) • SYP (Synaptophysin)
    |
    TP53 mutation • HER-2 amplification • MET amplification • STK11 mutation • PD-L1 negative • CDKN2A mutation • MET mutation • BRCA2 deletion • SMARCA4 mutation • BRCA1 deletion
    |
    PD-L1 IHC 22C3 pharmDx
    3ms
    Clinicopathological features of SMARCA4-deficient lung adenocarcinoma: a study of 42 cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
    It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.
    Journal • Retrospective data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1) • NAPSA (Napsin A Aspartic Peptidase)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • STK11 mutation • RET mutation • KEAP1 mutation • MET mutation • SMARCA4 mutation • NKX2-1 expression • TTF1 expression
    |
    PD-L1 IHC 22C3 pharmDx
    3ms
    Combining genomic biomarkers to guide immunotherapy in non-small cell lung cancer. (PubMed, Clin Cancer Res)
    The unexpected ICB responses in patients carrying resistance biomarkers in STK11, KEAP1 and EGFR were almost exclusively observed in patients with a high TMB. Considering these alterations in the context the TMB offered a highly specific combinatorial biomarker strategy for limiting overtreatment in NSCLC.
    Journal • Tumor mutational burden • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    TMB-H • STK11 mutation • TMB-L • KEAP1 mutation
    3ms
    TRITON: A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic Non-Small Cell Lung Cancer (NSCLC) Patients (clinicaltrials.gov)
    P3, N=280, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting
    Enrollment open
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    KRAS mutation • EGFR mutation • STK11 mutation • ALK fusion • KEAP1 mutation
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • Imfinzi (durvalumab) • Imjudo (tremelimumab) • pemetrexed
    3ms
    ARC-27: A Study of AB801 Monotherapy and Combination Therapy in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1, N=80, Recruiting, Arcus Biosciences, Inc. | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    EGFR mutation • STK11 mutation • ALK mutation
    |
    docetaxel • Yutuo (zimberelimab)
    4ms
    A phase II study to evaluate the safety and efficacy of anlotinib combined with toripalimab for advanced biliary tract cancer. (PubMed, Clin Transl Immunology)
    In patients with advanced BTC, the combination of anlotinib and toripalimab demonstrated remarkable anti-tumor potential, with increased objective response rates (ORR), longer overall survival (OS) and progression-free survival (PFS). Moreover, STK11 and CD8/Foxp3 may be as biomarkers that can predict the effectiveness of targeted therapy in combination with immunotherapy.
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • FOXP3 (Forkhead Box P3)
    |
    STK11 mutation
    |
    Focus V (anlotinib) • Loqtorzi (toripalimab-tpzi)
    4ms
    Genomic and Immunophenotypic Landscape of Acquired Resistance to PD-(L)1 Blockade in Non-Small-Cell Lung Cancer. (PubMed, J Clin Oncol)
    These findings highlight the genomic and immunophenotypic heterogeneity of ICI resistance in NSCLC, which will need to be considered when developing novel therapeutic strategies aimed at overcoming resistance.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • STK11 (Serine/threonine kinase 11) • JAK2 (Janus kinase 2) • KEAP1 (Kelch Like ECH Associated Protein 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • mTOR (Mechanistic target of rapamycin kinase) • B2M (Beta-2-microglobulin) • JAK1 (Janus Kinase 1) • CD3E (CD3 Epsilon Subunit Of T-Cell Receptor Complex)
    |
    STK11 mutation • MTOR mutation
    4ms
    STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis. (PubMed, Open Med (Wars))
    Subsequent rescue assays demonstrated that STK11 mutations hindered ferroptosis by impacting the synthesis of MUFAs in LUAD cells. This study provided evidence that STK11 mutations suppressed ferroptosis in LUAD cells by promoting MUFA synthesis, thus offering a novel research direction in the management of LUAD.
    Journal
    |
    STK11 (Serine/threonine kinase 11) • SLC7A11 (Solute Carrier Family 7 Member 11) • SCD (Stearoyl-CoA Desaturase)
    |
    STK11 mutation • STK11 expression
    4ms
    Identification of non-actionable mutations with prognostic and predictive value in patients with advanced or metastatic non-small cell lung cancer. (PubMed, Clin Transl Oncol)
    Our results provide evidence on the prognostic value of STK11, KEAP1, and CDKN2A/B mutations in patients with aNSCLC. Further research is required to better understand the implications of these findings on patient management and future trial design and treatment selection.
    Journal • IO biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KEAP1 (Kelch Like ECH Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • KRAS mutation • STK11 mutation • KEAP1 mutation • CDKN2A mutation
    4ms
    Caloric restriction and metformin selectively improved LKB1-mutated NSCLC tumor response to chemo- and chemo-immunotherapy. (PubMed, J Exp Clin Cancer Res)
    Our in vitro and in vivo preliminary studies confirm our hypothesis that the addition of metformin and CR is able to improve the antitumor activity of chemo and chemoimmunotherapy in LKB1 impaired tumors, exploiting their inability to overcome metabolic stress.
    Journal • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
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    KRAS mutation • STK11 mutation
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    metformin
    4ms
    DIRAS3 induces autophagy and enhances sensitivity to anti-autophagic therapy in KRAS-driven pancreatic and ovarian carcinomas. (PubMed, Autophagy)
    Treatment with chloroquine or the novel dimeric chloroquine analog DC661 significantly enhances DIRAS3-mediated inhibition of mutant KRAS tumor cell growth in vitro and in vivo. Taken together, our study demonstrates that DIRAS3 plays a critical role in regulating mutant KRAS-driven oncogenesis in PDAC and LGSOC.Abbreviations: AFR: autophagic flux reporter; ATG: autophagy related; CQ: chloroquine; DCFDA: 2'-7'-dichlorodihydrofluorescein diacetate; DIRAS3: DIRAS family GTPase 3; DOX: doxycycline; KRAS: KRAS proto-oncogene, LGSOC: low-grade serous ovarian cancer; MiT/TFE: microphthalmia family of transcription factors; NAC: N-acetylcysteine; PDAC: pancreatic ductal adenocarcinoma; ROS: reactive oxygen species; TFEB: transcription factor EB.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • DIRAS3 (DIRAS Family GTPase 3) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • TFEB (Transcription Factor EB 2)
    |
    KRAS mutation • STK11 mutation • KRAS wild-type • RAS wild-type
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    chloroquine phosphate
    4ms
    Endocrine tumors of the female reproductive tract. (PubMed, Mol Cell Endocrinol)
    An important consideration is the distinction of primary disease from metastatic malignancy. Genetic disorders including those caused by germline mutations of the FOXL2, GNAS, DICER1, STK11 and MEN1 genes can present with primary endocrine neoplasms of the female reproductive tract.
    Journal
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    STK11 (Serine/threonine kinase 11) • GNAS (GNAS Complex Locus) • DICER1 (Dicer 1 Ribonuclease III) • MEN1 (Menin 1) • FOXL2 (Forkhead Box L2)
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    STK11 mutation
    4ms
    Genomic landscape and actionable mutations of brain metastases derived from non-small cell lung cancer: A systematic review. (PubMed, Neurooncol Adv)
    These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.
    Review • Journal
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    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • KRAS G12C • EGFR L858R • EGFR T790M • STK11 mutation • KRAS G12
    4ms
    Phase I study of mTORC1/2 inhibitor sapanisertib in combination with metformin in patients with mTOR/AKT/PI3K pathway alterations and advanced solid malignancies. (PubMed, Cancer Res Commun)
    The safety profile of mTORC1/2 inhibitor sapanisertib in combination with metformin was generally tolerable, with anti-tumor activity observed in patients with advanced malignancies harboring PTEN/ AKT/mTOR pathway alterations.
    P1 data • Journal • Combination therapy • Metastases
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • STK11 (Serine/threonine kinase 11) • TSC1 (TSC complex subunit 1)
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    PTEN mutation • STK11 mutation • MTOR mutation
    |
    sapanisertib (CB-228) • metformin
    4ms
    Clinicopathological characteristics and treatment outcomes of advanced SMARCA4-deficient thoracic tumors. (PubMed, Cancer Med)
    SMARCA4-deficient thoracic tumors exhibit distinct characteristics from conventional NSCLCs, and PD-1 inhibitors show promise in treating advanced SMARCA4-deficient thoracic tumors.
    Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NCAM1 (Neural cell adhesion molecule 1) • NKX2-1 (NK2 Homeobox 1) • SYP (Synaptophysin)
    |
    TP53 mutation • KRAS mutation • PTEN mutation • STK11 mutation
    4ms
    TRITON: A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic Non-Small Cell Lung Cancer (NSCLC) Patients (clinicaltrials.gov)
    P3, N=280, Not yet recruiting, AstraZeneca | Trial primary completion date: Mar 2031 --> Aug 2027
    Trial primary completion date • Combination therapy • Metastases
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    KRAS mutation • EGFR mutation • STK11 mutation • ALK fusion • KEAP1 mutation
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • Imfinzi (durvalumab) • Imjudo (tremelimumab) • pemetrexed
    5ms
    A Phase II Trial of JDQ443 in KRAS G12C-Mutated NSCLC with PD-L1 Expression <1% or PD-L1 Expression ≥1% and an STK11 Co-Mutation (MTCS 2023)
    TBD
    P2 data • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12 • KRAS mutation + STK11 mutation • KRAS G12C + PD-L1 expression • PD-L1 expression + STK11 mutation
    |
    opnurasib (JDQ443)
    5ms
    KRAS G12C-mutant driven non-small cell lung cancer (NSCLC). (PubMed, Crit Rev Oncol Hematol)
    Evidence indicates that treatment with KRAS G12C inhibitors (sotorasib) triggers the MRAS:SHOC2:PP1C trimeric complex. Exploring these pathways as therapeutic targets and their impact on different chemotherapeutic agents (carboplatin, paclitaxel) is crucial. Comutations in STK11/LKB1 often co-occur with KRAS G12C, jeopardizing the effect of immune checkpoint (anti-PD1/PDL1) inhibitors.
    Review • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • HUWE1 (HECT UBA And WWE Domain Containing E3 Ubiquitin Protein Ligase 1)
    |
    KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12
    |
    carboplatin • paclitaxel • Lumakras (sotorasib)
    5ms
    LUNG-MAP Sub-Study: 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) (clinicaltrials.gov)
    P2; Trial completion date: Feb 2024 --> May 2024
    Trial completion date
    |
    STK11 (Serine/threonine kinase 11)
    |
    STK11 mutation
    |
    FoundationOne® CDx
    |
    Bavencio (avelumab) • Talzenna (talazoparib)
    5ms
    Characterization of the cachexia pathway in pancreatic ductal adenocarcinoma. (ASCO-GI 2024)
    This is the largest molecular and clinical characterization of the myostatin-activin cachexia pathway in PDAC. Our data show that increased activation of the myostatin-activin pathway is associated with immune mediators, lipid metabolism, and inflammatory gene activation. Activators and repressors are significant predictors of survival in PDAC, suggesting possible novel therapeutic targets.
    PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • SMAD4 (SMAD family member 4) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CCL2 (Chemokine (C-C motif) ligand 2) • IL1B (Interleukin 1, beta) • SMAD7 (SMAD Family Member 7) • ACVR2A (Activin A Receptor Type 2A) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • SMAD2 (SMAD Family Member 2) • SMAD3 (SMAD Family Member 3) • SMURF1 (SMAD Specific E3 Ubiquitin Protein Ligase 1) • SMURF2 (SMAD Specific E3 Ubiquitin Protein Ligase 2) • TGFBR1 (Transforming Growth Factor Beta Receptor 1) • ACVR1B (Activin A Receptor Type 1B) • ACVR2B (Activin A Receptor Type 2B)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • ARID1A mutation • STK11 mutation
    |
    MI Tumor Seek™