CD73 Is Regulated by the EGFR-ERK Signaling Pathway in Non-small Cell Lung Cancer
Background/Aim: Although EGFR tyrosine kinase inhibitors (TKIs) offer initial therapeutic benefits, the treatment of EGFR-mutant non-small cell lung cancer (NSCLC) remains challenging. While cancer immunotherapy has yielded promising results in various tumors, the response rate in EGFR-mutant NSCLC is typically low, likely due to the weak immunogenicity of these tumors.
Materials and Methods: In this study, we utilized both in vivo NSCLC datasets and in vitro cell culture models to explore the regulation of CD73 by EGFR.
Results: A significant correlation was observed between EGFR and CD73 expression in patient datasets, with EGFR-mutant tumors exhibiting higher CD73 levels compared to EGFR wild-type tumors. Treatment of EGFR-mutant NSCLC cell lines with EGFR RGT-018 TKIs resulted in a reduction in CD73 expression at both the mRNA and protein levels. Investigation of EGFR downstream signaling pathways revealed that the Ras-Raf-ERK pathway plays a key role in regulating CD73 expression, acting directly through ERK1/2 and independent of RSKs or MSKs.
Conclusion: These findings suggest potential new therapeutic avenues for treating oncogene-driven NSCLC, particularly by targeting the EGFR-CD73 signaling axis.