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    Association details:
    Biomarker:PIK3CA mutation
    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 2022
    Title:

    1120 / 10 - Tipifarnib potentiates the antitumor effects of PI3Ka blockade in HNSCC via convergent inhibition of mTOR activity

    Published date:
    03/09/2022
    Excerpt:
    ...we examined tipifarnib’s impact on growth of PIK3CA-altered HNSCC models in vitro and in vivo. In cell lines harboring PIK3CA mutation or amplification, tipifarnib reduced proliferation of both monolayer and spheroid cultures and when combined with alpelisib, induced cytotoxicity. Consistently, in PIK3CA mutant/amplified PDX models, the tipifarnib-alpelisib doublet led to deeper antitumor responses compared to alpelisib monotherapy.