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    BIOMARKER:

    HRAS Q61

    i
    Other names: HRAS, HRAS1, Harvey rat sarcoma viral oncogene homolog
    Entrez ID:
    3265
    Related biomarkers:
    Expression
    Mutation
    Others
    9ms
    Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer (clinicaltrials.gov)
    P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • EGF (Epidermal growth factor)
    |
    KRAS mutation • NRAS mutation • BRAF V600 • BRAF wild-type • RAS wild-type • HRAS mutation • KRAS G12 • NRAS Q61 • KRAS G13 • NRAS G12 • NRAS G13 • KRAS Q61 • HRAS Q61
    |
    Mekinist (trametinib)
    over1year
    Molecular and clinical characteristics of patients with KRAS mutated pancreatic ductal adenocarcinoma. (ASCO 2023)
    KRAS mt subtypes may confer different PDAC phenotypes. In our cohort, G12R is associated with improved OS while G12V correlates with worse prognosis in de novo metastatic disease. Additionally, there are differences in genomic variations and RNA expression between the KRAS mt subtypes.
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • KMT2C (Lysine Methyltransferase 2C) • KDM6A (Lysine Demethylase 6A) • RBM10 (RNA Binding Motif Protein 10)
    |
    KRAS mutation • KRAS G12D • KRAS G12V • KRAS wild-type • RAS wild-type • KRAS G12 • KRAS Q61 • HRAS Q61 • KRAS expression
    over1year
    Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer (clinicaltrials.gov)
    P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2023 --> Jan 2024
    Trial completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TG (Thyroglobulin)
    |
    KRAS mutation • NRAS mutation • BRAF V600 • BRAF wild-type • RAS wild-type • HRAS mutation • KRAS G12 • NRAS Q61 • KRAS G13 • NRAS G12 • NRAS G13 • KRAS Q61 • HRAS Q61
    |
    Mekinist (trametinib)
    almost2years
    RAS Mutations in Adult Acute Myeloid Leukemia (AML). Frequency, Mutational Spectrum, and Identification of a Comutation Bias for KRASK117 (TET2/ASXL1) (ASH 2022)
    Complex and miscellaneous karyotypes showed KRAS mutations more often. KRASK117N mutations were consistently associated with TET2 and ASXL1 mutations and mutually exclusive with NPM1 and DNMT3A.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • RAS (Rat Sarcoma Virus)
    |
    KRAS mutation • NRAS mutation • NPM1 mutation • DNMT3A mutation • RAS mutation • ASXL1 mutation • TET2 mutation • NRAS Q61K • NRAS Q61 • KRAS Q61 • HRAS K117N • HRAS Q61
    almost2years
    Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors (clinicaltrials.gov)
    P1, N=45, Recruiting, UNC Lineberger Comprehensive Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • CA 19-9 (Cancer antigen 19-9)
    |
    BRAF V600 • NF1 mutation • RAS mutation • KRAS G12 • NRAS Q61 • KRAS G13 • KRAS amplification • NRAS G12 • NRAS G13 • KRAS Q61 • HRAS Q61
    |
    Ibrance (palbociclib) • ulixertinib (BVD-523)
    2years
    Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors (clinicaltrials.gov)
    P1, N=45, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Oct 2023 --> Apr 2026 | Trial primary completion date: Oct 2022 --> Jul 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • CA 19-9 (Cancer antigen 19-9)
    |
    BRAF V600 • NF1 mutation • RAS mutation • KRAS G12 • NRAS Q61 • KRAS G13 • KRAS amplification • NRAS G12 • NRAS G13 • KRAS Q61 • HRAS Q61
    |
    Ibrance (palbociclib) • ulixertinib (BVD-523)
    over2years
    Genomic characteristics and clinical outcomes of HRAS-mutated urothelial bladder cancer (ESMO 2022)
    Our transcriptomic analysis suggests HRAS-Q61 mutations were associated with lower response to immunotherapy and leads to MAPK activation, as well as modulation of important TME pathways, possibly indicating a distinct biological and clinical phenotype. Our study provides rationale for therapeutic HRAS targeting in UBC.
    Clinical • Clinical data • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • KMT2D (Lysine Methyltransferase 2D)
    |
    PD-L1 expression • BRAF mutation • KMT2D mutation • HRAS mutation • NRAS Q61 • HRAS Q61 • HRAS wild-type
    over2years
    Tumor microenvironment (TME) of HRAS mutated non-small cell lung cancer (NSCLC) (ESMO 2022)
    In addition, HRAS Q61 was found to be correlated with worse prognosis in pts treated with pembro (HR = 2.779, 95% CI [1.04-7.423], p =0.03) but not G12 or G13, and displayed the highest MPAS score (p = 0.05), which had previously been demonstrated to indicate immune evasion...HRAS mt SCC also showed an immune-cold TME associated with high MAPK pathway activation and high LAG3 expression. This warrants further investigation, in particular in HRAS Q61 or HRAS mt SCC, with combination therapies targeting MAPK pathway or LAG3 protein.
    IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • CD4 (CD4 Molecule)
    |
    HRAS mutation • LAG3 expression • KRAS Q61 • HRAS Q61 • LAG3 elevation
    |
    Keytruda (pembrolizumab)