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    BIOMARKER:

    KEAP1 mutation

    i
    Other names: KEAP1, Kelch Like ECH Associated Protein 1, Cytosolic Inhibitor Of Nrf2, Kelch-Like Family Member 19, Kelch-Like Protein 19, KLHL19, INrf2, KEAP1 Delta C, KIAA0132, INRF2
    Entrez ID:
    9817
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    1d
    M25RIO: A short treatment with immunotherapy instead of radiotherapy in early-stage lung cancer (2025-524305-32-00)
    P1/2, N=30, Not yet recruiting, Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
    New P1/2 trial
    |
    PD-L1 (Programmed death ligand 1) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    STK11 mutation • KEAP1 mutation
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    Libtayo (cemiplimab-rwlc)
    3d
    miR-941 in extracellular vesicles confers anlotinib resistance via Keap1/Nrf2 axis and represents a therapeutic target in non-small cell lung cancer. (PubMed, Clin Transl Med)
    EV-derived miR-941 as a key driver of anlotinib resistance via the Keap1/Nrf2 pathway represent a promising non-invasive predictive biomarker and a potential therapeutic target for overcoming resistance in NSCLC.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • KEAP1 (Kelch Like ECH Associated Protein 1) • MCL1 (Myeloid cell leukemia 1)
    |
    KEAP1 mutation
    |
    Focus V (anlotinib)
    4d
    Curcumin improves bladder dysfunction in diabetic rats by attenuating oxidative stress via the Keap1/NRF2/HO-1 pathway. (PubMed, Transl Androl Urol)
    Histological analyses revealed attenuated bladder tissue fibrosis and apoptosis, concomitant with suppressed Keap1 and elevated expression of NRF2, HO-1, and SOD1 in the bladder tissue. Cur alleviates OS and thereby ameliorates DBD in diabetic rats by regulating the Keap1/NRF2/HO-1 pathway, which highlights its therapeutic potential for DBD.
    Preclinical • Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • HMOX1 (Heme Oxygenase 1) • CASP3 (Caspase 3) • SOD1 (Superoxide Dismutase 1)
    |
    KEAP1 mutation
    7d
    Clinicogenomic Landscape of Histologic Subtypes in Ovarian Cancer: Real-World Evidence From a Japanese Nationwide Cohort. (PubMed, JCO Precis Oncol)
    This large clinicogenomic study in an Asian population highlights unique mutational landscapes and survival associations, which may inform personalized treatment strategies.
    Retrospective data • Journal • HEOR • Real-world evidence • BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • KEAP1 (Kelch Like ECH Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • PIK3CA mutation • ARID1A mutation • CDKN2A deletion • KEAP1 mutation • NFE2L2 mutation
    7d
    Peri-Implant Gingival Undifferentiated SWI/SNF Complex-Deficient Tumor with Molecularly Confirmed Biallelic SMARCA4 Inactivation: Diagnostic Pitfalls and Genomic Characterization. (PubMed, Diagnostics (Basel))
    The patient initiated carboplatin-paclitaxel and achieved a partial response at one month with further shrinkage by four months. Rapidly enlarging peri-implant gingival masses should prompt timely biopsy and SWI/SNF marker testing when histology is high-grade and lineage-ambiguous. NGS-based molecular profiling confirms diagnosis, elucidates mechanism, and reveals actionable targets in this rare tumor class.
    Journal • Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KEAP1 (Kelch Like ECH Associated Protein 1) • MTAP (Methylthioadenosine Phosphorylase) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    TP53 mutation • TMB-H • CDKN2A deletion • MTAP deletion • KEAP1 mutation
    |
    Oncomine™ Comprehensive Assay Plus
    |
    carboplatin • paclitaxel
    9d
    Molecular and clinical characteristics of patients with non-small cell lung cancer (NSCLC) harboring KRAS Q61 mutations to assess therapeutic responses. (PubMed, Clin Cancer Res)
    KRAS Q61H and Q61L were the predominant mutational subtypes and demonstrated distinct molecular and clinical characteristics, with differences in co-mutational landscape and survival differences. Immunotherapy-based regimens were associated with more favorable outcomes compared to chemotherapy, particularly in patients with high PD-L1 expression, underscoring the importance of subtype-specific molecular characterization in clinical decision-making.
    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) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • PD-L1 overexpression • STK11 mutation • KEAP1 mutation • KRAS Q61
    9d
    Betaine induces ferroptotic stress by enhancing KEAP1-mediated NRF2 degradation in breast cancer cells. (PubMed, Cell Signal)
    BET may promote ferroptosis-associated cell death and suppress breast cancer cell malignant phenotypes, potentially through modulation of the KEAP1/NRF2/xCT/GPX4 pathway. These findings suggest a possible therapeutic relevance of BET in breast cancer, although further in vivo and clinical validation is required.
    Journal
    |
    KEAP1 (Kelch Like ECH Associated Protein 1) • GPX4 (Glutathione Peroxidase 4)
    |
    KEAP1 mutation • NFE2L2 mutation
    11d
    Targeting NRF2 addiction in cancer: synthetic lethal strategies beyond direct inhibition. (PubMed, Front Cell Dev Biol)
    This review focuses on targeting NRF2-driven metabolic dependencies as synthetic lethal vulnerabilities, spanning pathways such as glutaminolysis, redox imbalance, cystine metabolism, nucleotide biosynthesis and ER proteostasis. We also highlight emerging strategies, including allosteric KEAP1 activators, and discuss key challenges in translating these approaches into effective therapies.
    Review • Journal
    |
    KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
    |
    KEAP1 mutation • NFE2L2 mutation
    17d
    IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=54, Recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2026 --> Jun 2028 | Trial primary completion date: May 2026 --> Mar 2028
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • PD-1 (Programmed cell death 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
    |
    PIK3CA mutation • PTEN mutation • ARID1A mutation • STK11 mutation • KEAP1 mutation • NFE2L2 mutation
    |
    Avastin (bevacizumab) • paclitaxel • Truqap (capivasertib) • IPN60090
    24d
    STK11 as an Emerging Biomarker in Non-Small Cell Lung Cancer. (PubMed, Curr Oncol)
    Beyond immunotherapy, STK11 mutations confer poor outcomes across targeted therapies, including KRAS G12C inhibitors, with KEAP1 co-mutation serving as a strong negative predictor of efficacy. In this review we present an overview of STK11 function and its role in tumor biology, highlight the prognostic and predictive potential of STK11 mutations in the context of NSCLC treatment and summarize the emerging treatment strategies.
    Review • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
    |
    PD-L1 expression • KRAS mutation • STK11 mutation • KEAP1 mutation
    25d
    Expression of LIFR in tumor and SHOC2, YAP1 in plasma mRNA as potential biomarkers in KRAS G12C NSCLC. (PubMed, Sci Rep)
    In plasma, twelve genes were consistently detected, and SHOC2, YAP1, LZTR1, RGS3, and ZDHHC7 were significantly upregulated at week 6. Low tumor LIFR expression was associated with poorer survival, supporting its potential as a prognostic biomarker and highlighting the feasibility of plasma-based gene expression monitoring.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • YAP1 (Yes associated protein 1) • LIFR (LIF Receptor Subunit Alpha) • ENO1 (Enolase 1) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)
    |
    TP53 mutation • KRAS mutation • KRAS G12C • STK11 mutation • KRAS wild-type • KEAP1 mutation • RAS wild-type • KRAS G12
    27d
    Targeted suppression of SPP1 inhibits tumor invasion and metastasis in NRF2 hyperactivated cisplatin resistant HNSCC. (PubMed, J Transl Med)
    Targeting dysregulated SPP1 improved cisplatin sensitivity and suppressed tumor invasion and metastasis in NRF2-hyperactivated HNSCC, underscoring the therapeutic potential of SPP1 inhibitors to improve patient outcomes.
    Journal
    |
    KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • SPP1 (Secreted Phosphoprotein 1)
    |
    KEAP1 mutation • NFE2L2 mutation
    |
    cisplatin