Importantly, inactivation of GPCR related effectors, such as RIC8A, PKN2, GNB2 (encoding Gβ2 subunit) or GNA13 (encoding Gα13 subunit), strongly synergized with EGFR inhibition in EGFR-mutant NSCLC cells, revealed by our CRISPR screen. This evidence concerns the gene PKN2 and non-small cell lung carcinoma.