Challenge and countermeasures for EGFR targeted therapy in non-small cell lung cancer

Lung cancer causes the highest mortality compared to other cancers in the world according to the latest WHO reports. Non-small cell lung cancer (NSCLC) contributes about 85% of total lung cancer cases. An extensive number of risk factors are attributed to the progression of lung cancer. Epidermal growth factor receptor (EGFR), one of the most frequently mutant driver genes, is closely involved in the development of lung cancer through regulation of the PI3K/AKT and MAPK pathways. As a representative of precision medicine, EGFR-tyrosine kinase inhibitors (TKIs) targeted therapy significantly relieves the development of activating mutant EGFR-driven NSCLC. However, treatment with TKIs facilitates the emergence of acquired resistance that continues to pose a significant hurdle with respect to EGFR targeted therapy. In this review, the development of current approved EGFR-TKIs as well as the related supporting clinical trials are summarized and discussed. Mechanisms of action and resistance were addressed respectively, which serve as important guides to understanding acquired resistance. We also explored the corresponding combination treatment options according to different resistance mechanisms. Future challenges include more comprehensive characterization of unclear resistance mechanisms in different populations and the development of more efficient and precision synthetic therapeutic strategies.

Automated summary

Lung cancer is the most deadly cancer worldwide, with non-small cell lung cancer (NSCLC) being the main type and EGFR as a key driver gene. Despite the effectiveness of EGFR-tyrosine kinase inhibitors in targeted therapy, acquired resistance remains a significant challenge, prompting the exploration of combination treatment options.