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    Association details:
    Biomarker:KRAS G12D
    Cancer:Non Small Cell Lung Cancer
    Drug:Mekinist (trametinib) (MEK inhibitor) +
    Tagrisso (osimertinib) (EGFR inhibitor) +
    buparlisib (AN2025) (PI3K inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    Ther Adv Med Oncol
    Title:

    Molecular landscape of osimertinib resistance in patients and patient-derived preclinical models

    Published date:
    02/26/2022
    Excerpt:
    A patient-derived xenograft established from osimertinib-resistant patient revealed KRAS p.G12D mutation which could be overcome with combination of osimertinib, trametinib, and buparlisib....For a PDX harboring acquired KRAS p.G12D mutation, we investigated whether combination of osimertinib, MEK inhibitor (trametinib), and PI3K inhibitor (buparlisib) could reverse resistance. The combination of osimertinib, trametinib, and buparlisib led to significant tumor regression compared with osimertinib, buparlisib, trametinib, or buparlisib plus trametinib (Figure 6(c)).
    DOI:
    https://doi.org/10.1177/17588359221079125