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    BIOMARKER:

    HER-2 V777L + PIK3CA H1047R

    i
    Other names: ERBB2, CD340, HER-2, HER2, NEU, NGL, V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2, PIK3CA, Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, Phosphoinositide-3-kinase, catalytic, alpha polypeptide, Serine/threonine protein kinase PIK3CA, PtdIns-3-kinase subunit P110-alpha, PI3K-alpha, Phosphatidylinositol-4,5-bisphosphate 3-kinase 110 KDa catalytic subunit alpha, Phosphatidylinositol 3-kinase, Catalytic, 110-KD, alpha, PI3-kinase P110 subunit alpha, PI3-kinase subunit alpha, PtdIns-3-kinase subunit alpha, PI3Kalpha, P110alpha, PI3K
    Entrez ID:
    2064; 5290
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    over1year
    Breast cancer mutations HER2 V777L and PIK3CA H1047R activate the p21-CDK4/6 -Cyclin D1 axis driving tumorigenesis and drug resistance. (PubMed, Cancer Res)
    We validated both the neratinib plus trastuzumab deruxtecan and neratinib plus palbociclib combinations using a human breast cancer patient-derived xenograft with very similar HER2 and PIK3CA mutations. Further, these two drug combinations effectively treated spontaneous lung metastasis in syngeneic mice transplanted with HP breast cancer organoids. Both of these drug combinations are being tested in phase 1 clinical trials and this study provides valuable preclinical evidence for them.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDH1 (Cadherin 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    TP53 mutation • PIK3CA mutation • HER-2 mutation • PIK3CA H1047R • HER-2 V777L • CCND1 expression • HER-2 V777L + PIK3CA H1047R • PIK3CA mutation + ER mutation
    |
    Ibrance (palbociclib) • Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)