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    Association details:
    Biomarker:HRAS overexpression
    Cancer:Squamous Cell Carcinoma of Head and Neck
    Drug:Piqray (alpelisib) (PIK3CA inhibitor) +
    Zarnestra (tipifarnib) (CXCL12 inhibitor, Farnesyl transferase inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    Cancer Res
    Title:

    Tipifarnib potentiates the antitumor effects of PI3Kα inhibition in PIK3CA- and HRAS-dysregulated HNSCC via convergent inhibition of mTOR activity

    Published date:
    06/20/2023
    Excerpt:
    Based on these findings, the KURRENT-HN trial was launched to evaluate the effectiveness of this combination in PIK3CA-mutant/amplified and/or HRAS-overexpressing R/M HNSCC….Preliminary evidence supports the clinical activity of this molecular biomarker-driven combination therapy. Combined alpelisib and tipifarnib has potential to benefit >45% of R/M HNSCC patients.
    DOI:
    10.1158/0008-5472.CAN-23-0282
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    AACR-NCI-EORTC 2022
    Title:

    HNSCCs overexpressing wild-type HRAS are sensitive to combined tipifarnib and alpelisib treatment

    Published date:
    10/12/2022
    Excerpt:
    ... we explored if dual inhibition of these pathways with tipifarnib and alpelisib would be an effective anti-tumor strategy...In vivo, combination therapy induced deeper antitumor responses in HNSCC PDXs with HRAS overexpression +/- co-occurring mutations in PIK3CA.