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  P73 - Tumor Biology and Systems Biology - Basic and Translational Science - RTK/FGFR (ID 209)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Tumor Biology and Systems Biology - Basic and Translational Science
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 35891

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    P73.03 - A Kinome CRISPR Screen in FGFR-Amplified Lung Cancer (ID 2472)

    00:00 - 00:00  |  Presenting Author(s): Zhang Yang
    • Abstract
    • Slides

    Introduction
    

    Oncogenic alterations in fibroblast growth factor receptor (FGFR) are frequent, but therapeutic targeting of FGFR-driven cancers remains an unmet challenge in clinical oncology in that FGFR inhibitors as a single agent are inevitably limited by poor responsiveness and/or compensatory activation of various acquired resistance mechanisms.

    Methods
    

    We performed kinome CRISPR/Cas9 screens to identify genetic determinants that limit efficacy of FGFR-targeted therapy in FGFR-mutant squamous lung carcinoma (SQLC).

    Results
    

    We identify several kinases including polo-like kinase I (PLK1) as key determinants of sensitivity to AZD4547, a selective FGFR inhibitor currently investigated in phase III clinical trials. We provided evidence showing that genetic and pharmacological inhibition of PLK1 synergistically enhances the effect of FGFR inhibitors in FGFR-amplified lung SQLC.

    Conclusion
    

    CRISPR/Cas9 screening is a powerful tool to uncover genetic determinants underlying drug sensitivity in cancer.

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