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    BIOMARKER:

    KRAS G13C

    i
    Other names: KRAS, KRAS1, KRAS2, Kirsten rat sarcoma viral oncogene homolog
    Entrez ID:
    3845
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    1year
    Rare presentation and unconventional treatment of Rosai-Dorfman disease. (PubMed, BMJ Case Rep)
    We present a case of a man in his late 50s with RDD who experienced worsening cytopenias, including severe neutropenia and respiratory distress, despite an initial positive response to steroids, rituximab and lenalidomide. Sirolimus was initiated and led to complete radiological remission of the disease. This case adds strength to the growing evidence supporting the efficacy of sirolimus in refractory RDD cases.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
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    KRAS mutation • EZH2 mutation • KRAS G13 • KRAS G13C
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    Rituxan (rituximab) • lenalidomide • sirolimus
    1year
    KRAS mutations in pulmonary adenocarcinomas (ECP 2024)
    KRAS is an attractive therapeutic strategy due to its high prevalence and its role in initiating and sustaining tumour growth. Approval of KRAS G12C inhibitors in locally advanced or metastatic NSCLC has brought hope to many patients. Studies show that non G12C KRAS mutation are found in 53% of adenocarcinomas.
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • GNAS (GNAS Complex Locus)
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    TP53 mutation • KRAS mutation • BRAF mutation • HER-2 amplification • KRAS G12D • PTEN mutation • KRAS G12V • MET exon 14 mutation • ALK mutation • KRAS G12A • FGFR3 amplification • KRAS G13C
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    Oncomine Precision Assay
    over1year
    Monoallelic KRAS (G13C) mutation triggers dysregulated expansion in induced pluripotent stem cell-derived hematopoietic progenitor cells. (PubMed, Stem Cell Res Ther)
    Our findings indicate that a monoallelic oncogenic KRAS can confer dysregulated expansion characteristics to non-transformed HPCs, which may constitute a pathological condition in RALD hematopoiesis. The use of iPSC-based screening platforms will lead to discovering treatments that enable selective inhibition of RAS-mutated HPC clones.
    Journal • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
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    KRAS mutation • KRAS wild-type • RAS mutation • RAS wild-type • KRAS G13 • KRAS G13C
    over1year
    Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases. (PubMed, ESMO Open)
    In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.
    Journal
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    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS G12R • KRAS G12A • KRAS G12 • KRAS G12S • KRAS Q61H • KRAS A146T • KRAS A146V • KRAS G13A • KRAS G13C
    over1year
    Top-Down Proteomic Assay to Evaluate KRAS4B-Compound Engagement. (PubMed, Anal Chem)
    We present two applications to demonstrate the capabilities of our assay: maleimide-biotin labeling of a KRAS4BG12D cysteine mutant panel and treatment of three KRAS4B proteins (WT, G12C, and G13C) with small molecule compounds. Our results show the time- or concentration-dependence of KRAS4B-compound engagement in context of the intact protein molecule while directly mapping the compound binding site.
    Journal
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    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12D • KRAS wild-type • RAS wild-type • KRAS G12 • KRAS G13C
    2years
    BRAF Mutation Heterogeneity Detected Using Circulating Tumor DNA Sequencing in Synchronous Colon Cancer: A Case Report. (PubMed, Cancer Diagn Progn)
    Next, we performed next-generation sequencing on circulating tumor DNA from the patient's plasma (Foundation One Liquid CDx), which revealed the V600E mutation of BRAF, suggesting that there was genetic heterogeneity among the synchronized primary lesions, one of which was responsible for the chemo-refractory rapid-growing liver metastases. Genetic profiling with liquid biopsy at the time of recurrence and metastasis may be useful in patients with multiple synchronous cancers because there is less heterogeneity between primary and metastatic sites.
    Journal • MSi-H Biomarker • Circulating tumor DNA
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)
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    BRAF V600E • MSI-H/dMMR • BRAF mutation • BRAF V600 • BRAF wild-type • KRAS G13 • KRAS G13C
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    FoundationOne® Liquid CDx
    over2years
    A Case of Rosai‑Dorfman Disease, Associated With KRAS 13C, POLE, and NDE1 Mutations, Masquerading as Chronic Myelomonocytic Leukemia: Complex Management Paradigm (SOHO 2023)
    A 57-year-old man with RDD developed worsening cytopenias and respiratory distress after his initial response to rituximab, steroids, and lenalidomide. NGS is likely to be helpful for the work-up and management of RDD. We found potential novel therapeutic targets in RDD, such as KRAS G13C and POLE mutations.
    Clinical
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    KRAS (KRAS proto-oncogene GTPase) • POLE (DNA Polymerase Epsilon)
    |
    KRAS mutation • POLE mutation • KRAS G13 • KRAS G13C
    |
    Rituxan (rituximab) • lenalidomide
    over2years
    RAS-precision medicine trans-atlantic partnership: Comparative analysis of KRAS codon 12 and 13 mutations in non-small cell lung cancer (ESMO 2023)
    These preclinical results indicate unique therapeutic vulnerabilities across allelic subgroups. RNA-sequencing and kinome profiling will allow us to further characterise these mutations in NSCLC.
    Licensing / partnership
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    KRAS (KRAS proto-oncogene GTPase) • NF1 (Neurofibromin 1) • RAS (Rat Sarcoma Virus)
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    KRAS mutation • KRAS G12C • KRAS G12D • KRAS wild-type • NF1 mutation • KRAS G13D • RAS wild-type • KRAS G12 • KRAS G13 • KRAS G13C • EPCAM expression • KRAS expression
    over2years
    Prevalence of KRAS Subtype Alterations in Non-Small Cell Lung Cancer (NSCLC) with Brain Metastases (IASLC-WCLC 2023)
    This study details the most prevalent KRAS alterations and co-mutations among KRASalt NSCLC. KRAS p.G12C was the most frequently observed alteration and co-mutations were found in TP53, LRP1B, STK11, KEAP1, and CDKN2A. Our findings have therapeutic implications as co-alterations with STK11/KEAP1 are associated with worse outcomes.
    PD(L)-1 Biomarker • IO biomarker
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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) • KEAP1 (Kelch Like ECH Associated Protein 1) • LRP1B (LDL Receptor Related Protein 1B)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • EGFR L858R • KRAS G12D • KRAS G12V • STK11 mutation • KRAS G12A • KRAS G12 • KRAS G13 • KRAS G13C • KRAS V12
    over2years
    Molecular Characterization of Non-small Cell Lung Cancer in People Living with HIV or Solid Organ Transplants (IASLC-WCLC 2023)
    The identification of targetable genomic alterations in tumors from individuals living with HIV and solid organ transplant recipients underscores the importance of comprehensive molecular testing in these patient populations. While important markers of immunotherapy response (PD-L1, TMB) were similar, different immune characteristics were identified. Further research is necessary to fully understand the molecular profiles of lung cancer in individuals with HIV and solid organ transplant.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    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) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • KDM5C (Lysine Demethylase 5C)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • KRAS G12C • NRAS mutation • PIK3CA mutation • HER-2 mutation • KRAS G12D • PTEN mutation • KRAS G12V • MET exon 14 mutation • STK11 mutation • KRAS G12 • KRAS G13 • NRAS G12D • LAG3 expression • NRAS G13 • KRAS G13C
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    over2years
    Clinical Impact of Next-Generation Sequencing in KRAS-Mutated Non-Small Cell Lung Cancer Patients: a Single-Center Experience (IASLC-WCLC 2023)
    The clinicopathological characteristics of included patients were consistent with the published literature. In the majority of KRAS-mutated patients included in this study, the use of NGS allowed for the detection of additional genetic alterations with potential clinical significance.
    Clinical • Next-generation sequencing • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)
    |
    KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12 • KRAS G12S • KRAS G13 • KRAS G13C
    over2years
    Distant Metastasis Pattern and Baseline Clinicopathological Features from a Real-World KRAS G12C Mutant Cohort of Advanced NSCLC Patients (IASLC-WCLC 2023)
    In our observational study the distribution of KRAS mutational status, its mutual exclusion with other concomitant driver mutations, and the strong association with smoking were consistent with data from literature. The G12C subgroup showed a different metastasis pattern with greater number of metastasis sites and higher incidence of brain metastases at the time of diagnosis compared to non-G12C patients. Despite the limited sample size, these results suggest that KRAS mutant patients represent a highly heterogeneous population and underline the need of better characterization of these patients to tailor treatment strategies.
    Clinical • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS wild-type • RAS wild-type • KRAS G12 • KRAS G13 • KRAS Q61H • KRAS G13C