Diverse perspectives on proteomic posttranslational modifications to address EGFR-TKI resistance in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the main histological subtype of lung cancer. For locally advanced and advanced NSCLC, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-targeted therapy has been the first choice for NSCLC patients with EGFR mutations. TKIs, as targeted drugs, inhibit kinase activity and autophosphorylation by competitively binding to the ATP binding site of the EGFR tyrosine kinase domain, which blocks the signal transduction mediated by EGFR and thus inhibits the proliferation of tumor cells. However, drug resistance to TKIs is inevitable. EGFR is also a highly glycosylated receptor tyrosine kinase, and a wide range of crosstalk occurs between phosphorylation and glycosylation. Therefore, can the phosphorylation state be altered by glycosylation to improve drug resistance? In this review, we summarize phosphorylation, glycosylation and the crosstalk between these processes as well as the current research status and methods. We also summarize the autophosphorylation and glycosylation sites of the EGFR protein and their crosstalk. By exploring the relationship between EGFR glycosylation and autophosphorylation in targeted TKI therapy, we find that research on EGFR glycosylation is crucial for targeted NSCLC treatment and will become a research direction for identifying potential targets related to regulating TKI drug sensitivity.