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    Association details:
    Biomarker:EGFR mutation
    Cancer:Non Small Cell Lung Cancer
    Drug:SHP099 (PTPN11 inhibitor) +
    SX-682 (CXCR2 antagonist, CXCR1 antagonist)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    Cancer Discov
    Title:

    Combined SHP2(SHP099)/CXCR1/2(SX682) inhibition depleted a specific cluster of S100a8/9high gMDSCs, generated Klrg1+ CD8+ effector T cells with a strong cytotoxic phenotype but expressing the checkpoint receptor NKG2A, and enhanced survival in Kras- and Egfr-mutant models. Our results argue for testing RAS/ERK pathway/CXCR1/2/NKG2A inhibitor combinations in NSCLC patients.

    Published date:
    08/08/2021
    Excerpt:
    Combined SHP2(SHP099)/CXCR1/2(SX682) inhibition depleted a specific cluster of S100a8/9high gMDSCs, generated Klrg1+ CD8+ effector T cells with a strong cytotoxic phenotype but expressing the checkpoint receptor NKG2A, and enhanced survival in Kras- and Egfr-mutant models. Our results argue for testing RAS/ERK pathway/CXCR1/2/NKG2A inhibitor combinations in NSCLC patients.
    DOI:
    10.1158/2159-8290.CD-21-0369