Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1

摘要: Summary Patients with EGFR -mutant lung adenocarcinomas (LUADs) who initially respond to first-generation tyrosine kinase inhibitors (TKIs) develop resistance these drugs. A combination of the irreversible TKI afatinib and antibody cetuximab can be used overcome TKIs; however, this drug eventually emerges. We identified activation mTORC1 signaling pathway as a mechanism dual inhibition in mouse models. The addition rapamycin reversed in vivo. Analysis afatinib-plus-cetuximab-resistant biopsy specimens revealed presence genomic alterations genes that modulate signaling, including NF2 TSC1 . These findings pinpoint enhanced plus identify mechanisms lead pathway, revealing potential therapeutic strategy for treating patients