Opportunities and challenges of co-targeting epidermal growth factor receptor and autophagy signaling in non-small cell lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are a standard therapy for patients with non-small cell lung cancer (NSCLC) with sensitive mutations. However, acquired resistance emerges following a median of 6-12 months. Several studies demonstrated that EGFR-TKI-induced tumor microenvironment stresses and autophagy are important causes of resistance. The current review summarizes the molecular mechanisms involved in EGFR-mediated regulation of autophagy. The role of autophagy in EGFR-TKI treatment, which may serve a role in protection or cell death, was discussed. Furthermore, co-inhibiting EGFR and autophagy signaling as a rational therapeutic strategy in the treatment of patients with NSCLC was explored.