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    BIOMARKER:

    CDKN2A mutation + BRAF V600E

    i
    Other names: CDKN2A, ARF, CDK4I, CDKN2, CMM2, INK4, INK4a, MLM, MTS1, p14, p14ARF, p16, p16INK4a, p19, p19Arf, Cyclin-dependent kinase inhibitor 2A, BRAF, B-raf proto-oncogene, B-raf proto-oncogene, Serine/threonine kinase, V-Raf murine sarcoma viral oncogene homolog B, Serine/threonine-protein kinase B-Raf, Proto-oncogene B-Raf, BRAF1, RAFB1, B-raf proto-oncogene Serine/threonine-protein kinase, Murine sarcoma viral (V-Raf) oncogene homolog B1, B-raf serine/threonine-protein, 94 KDa B-raf protein, B-RAF1
    Entrez ID:
    673; 1029
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    Associations

    News

    Trials
    2years
    The first-in-class ERK inhibitor ulixertinib (BVD-523) shows activity in MAPK-driven pediatric low-grade glioma models as single agent and in combination with MEK inhibitors or senolytics (AACR 2022)
    Furthermore, ulixertinib treatment slowed tumor growth and significantly increased survival in NSG mice with orthotopic BT40 xenografts.Ulixertinib showed indications for anti-proliferative synergy in vitro, according to the Loewe and Bliss independence models, in combination with MEK inhibitors (trametinib, binimetinib) or senolytics (navitoclax, A1331852). Combinations with chemotherapy (carboplatin, vinblastine) were at most additive...The combination of ulixertinib with navitoclax was further investigated in the BT40 PDX mouse model, where tumor growth and survival were comparable to ulixertinib monotherapy.In conclusion, our data indicate a strong potential for ulixertinib as a clinically relevant therapeutic option for the treatment of pLGG to be further investigated in upcoming clinical trials. Potential synergism with MEK inhibitors and senolytics was noted and warrants further investigation.
    Clinical • Combination therapy
    |
    BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    BRAF V600E • BRAF V600 • CDKN2A deletion • CDKN2A mutation • BRAF fusion • CDKN2A mutation + BRAF V600E
    |
    Mekinist (trametinib) • carboplatin • Mektovi (binimetinib) • navitoclax (ABT 263) • ulixertinib (BVD-523) • A-1331852 • vinblastine