SHP2 inhibition enhances the anticancer effect of Osimertinib in EGFR T790M mutant lung adenocarcinoma by blocking CXCL8 loop mediated stemness

Abstract Background Additional epidermal growth factor receptor (EGFR) mutations confer the drug resistance to generations of EGFR targeted tyrosine kinase inhibitor (EGFR-TKI), posing a major challenge developing effective treatment lung adenocarcinoma (LUAD). The strategy combining EGFR-TKI with other synergistic or sensitizing therapeutic agents are considered promising approach in era precision medicine. Moreover, role and mechanism SHP2, which is involved cell proliferation, cytokine production, stemness maintenance resistance, has not been carefully explored Methods To evaluate impact SHP2 on efficacy T790M mutant LUAD cells Osimertinib, inhibition was tested Osimertinib treated cells. Cell proliferation were modified RNA sequencing performed explore promoted stemness. Results This study demonstrated that high expression level correlates poor outcome patients, enriched resistant suppressed damaged LUAD. facilitates secretion CXCL8 from cells, through CXCL8-CXCR1/2 positive feedback loop promotes tumorigenesis. Our results further show mediates ERK-AKT-NF?B GSK3?-?-Catenin signaling Conclusions data revealed enhances anti-cancer effect by blocking mediated stemness, may help provide an alternative option enhance clinical osimertinib patients.