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    BIOMARKER:

    HER-2 T798I

    i
    Other names: ERBB2, CD340, HER-2, HER2, NEU, NGL, V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2
    Entrez ID:
    2064
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    8ms
    Acquired secondary HER2 mutations enhance HER2/MAPK signaling and promote resistance to HER2 kinase inhibition in breast cancer. (PubMed, Cancer Res)
    HER2 mutations drive the growth of a subset of breast cancers and are targeted with HER2 tyrosine kinase inhibitors (TKI) such as neratinib...Cells expressing double HER2 mutations exhibited resistance to most HER2 TKIs but retained sensitivity to mobocertinib and poziotinib...Double-mutant cells showed enhanced MEK/ERK signaling, which was blocked by combined inhibition of HER2 and MEK. Together, these findings reveal the driver function of secondary HER2 mutations in resistance to HER2 inhibition and provide a potential treatment strategy to overcome acquired resistance to HER2 TKIs in HER2-mutant breast cancer.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 mutation • HER-2 expression • HER-2 L755S • HER-2 T798I • HER-2 T862A
    |
    Nerlynx (neratinib) • Pozenveo (poziotinib) • Exkivity (mobocertinib)
    3years
    [VIRTUAL] A phase II trial of neratinib (NER) or NER plus fulvestrant (FUL) (N+F) in HER2 mutant, non-amplified (HER2mut) metastatic breast cancer (MBC): Part II of MutHER (AACR 2021)
    Introduction: The irreversible pan-HER inhibitor NER showed modest single agent activity for HER2mut MBC in Part I of MutHER trial. NER, or N+F, is active for HER2mut MBC with good tolerability. Adding trastuzumab at PD induced further response, supporting dual HER2 blockade for HER2mut MBC.
    P2 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDH1 (Cadherin 1)
    |
    TP53 mutation • ER positive • PIK3CA mutation • HER-2 mutation • HER-2 T798I
    |
    Guardant360® CDx
    |
    Herceptin (trastuzumab) • Nerlynx (neratinib) • fulvestrant
    over4years
    A Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies (clinicaltrials.gov)
    P2, N=150, Recruiting, Spectrum Pharmaceuticals, Inc | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • HER-2 amplification • EGFR L858R • HER-2 mutation • EGFR T790M • HER-2 exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • HER-2 S310F • HER-2 V777L • EGFR E709K • HER-2 I655V • HER-2 L869R • HER-2 V842I • EGFR P596L • EGFR R222C • HER-2 T798M • EGFR E746 • HER-2 D769H • HER-2 R678Q • HER-2 T798I • HER-2 mutation + HER-2 T798I • EGFR V774M
    |
    Pozenveo (poziotinib)