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    BIOMARKER:

    PIK3CA mutation + AKT1 mutation + PTEN mutation

    i
    Other names: PTEN, Phosphatase and tensin homolog, Mutated In Multiple Advanced Cancers 1, Phosphatase And Tensin Homolog, Phosphatidylinositol 3,4,5-Trisphosphate 3-Phosphatase And Dual-Specificity Protein Phosphatase PTEN, MMAC1, TEP1, MMAC1 Phosphatase And Tensin Homolog Deleted On Chromosome 10, Mitochondrial Phosphatase And Tensin Protein Alpha, Phosphatase And Tensin-Like Protein, Protein Tyrosine Phosphatase, Mitochondrial PTENalpha, PTENbeta, PTEN1, CWS1, GLM2, MHAM, 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, AKT1, AKT, PKB, PRKBA, RAC, V-akt murine thymoma viral oncogene homolog 1, AKT2, V-akt murine thymoma viral oncogene homolog 2, AKT3, PKBG, PRKBG, RAC-gamma, V-akt murine thymoma viral oncogene homolog 3
    Entrez ID:
    5290; 5728; 207
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    2ms
    PF-07248144, a first-in-class KAT6 inhibitor, in patients with HR+ HER2− metastatic breast cancer: Updated results from phase 1 dose expansion study (SABCS 2024)
    PF-07248144 in combination with fulv demonstrated an acceptable safety profile and promising efficacy in pts with ER+ HER2− mBC post CDK4/6i and ET. Antitumor activity was observed irrespective of ESR1 and PIK3CA/AKT1/PTEN mutation status, endocrine sensitivity or resistance, duration of prior CDK4/6i treatment (12 mos), prior fulvestrant treatment, and 2L or later line therapy. These findings suggest that PF-07248144 in combination with ET may potentially overcome endocrine resistance and CDK4/6i resistance and provide a novel mechanism to address high unmet medical need in HR+ mBC after prior CDK4/6i and ET.
    Clinical • P1 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • KAT6A (Lysine Acetyltransferase 6A) • KAT6B (Lysine Acetyltransferase 6B)
    |
    PIK3CA mutation • PTEN mutation • ER mutation • PIK3CA mutation + AKT1 mutation + PTEN mutation
    |
    Guardant360® CDx
    |
    fulvestrant • PF-07248144
    2ms
    Efficacy of trastuzumab deruxtecan (T-DXd) in patients with metastatic lobular breast cancer with or without HER2 mutations: the MSKCC experience (SABCS 2024)
    The SUMMIT trial demonstrated meaningful activity of neratinib + fulvestrant + trastuzumab in patients with HR+, HER2 non-amplified, HER2-mutant MBC. In patients with mILC and HER2 mutation, there was a trend toward longer TTP with T-DXd. Genomic data could aid in prognostication in patients with mILC treated with T-DXd. These findings warrant confirmation in larger cohorts.
    Clinical • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    HER-2 negative • PIK3CA mutation • HER-2 mutation • HER-2 expression • PTEN mutation • PIK3CA mutation + PTEN mutation • PIK3CA mutation + AKT1 mutation + PTEN mutation
    |
    MSK-IMPACT
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • fulvestrant
    over1year
    Phase 1b study of pan-AKT inhibitor vevorisertib alone or with paclitaxel or fulvestrant in PIK3CA/AKT/PTEN-mutated advanced solid tumors. (PubMed, Cancer)
    Vevorisertib alone or with paclitaxel or fulvestrant had a manageable safety profile, and vevorisertib alone or with paclitaxel had minimal to modest antitumor activity in this patient population with PIK3CA/AKT/PTEN-mutated advanced solid tumors.
    P1 data • Clinical Trial,Phase I • Journal • Metastases
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation • PTEN mutation • PIK3CA mutation + AKT1 mutation + PTEN mutation
    |
    paclitaxel • fulvestrant • vevorisertib (ARQ 751)