Abstract
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. We performed kinome CRISPR/Cas9 screens to identify genetic determinants that limit efficacy of FGFR-targeted therapy in FGFR-mutant squamous lung carcinoma (SQLC). 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. CRISPR/Cas9 screening is a powerful tool to uncover genetic determinants underlying drug sensitivity in cancer.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
