Investigating the Clinical Impact of EGFR Mutations in Non-Small Cell Lung Cancer: Mutation-Specific Pathogenesis and Targeted Therapy Resistance

One of the main causes of death that is caused by cancer globally remains non-small cell lung cancer (NSCLC). An activating mutation in the Epidermal Growth Factor Receptor (EGFR) gene, in particular, exon 19 deletions and the L858R point mutation, is present in a large proportion of NSCLC cases. These changes cause further signaling pathways to be consistently activated. This activation can result in unregulated cell division and tumor growth. EGFR TKIs like gefitinib, erlotinib, and osimertinib have helped change treatment; however, secondary mutations like T790M or C797S remain a serious clinical obstacle. This study evaluates resistance patterns to current TKIs, maps the effects of specific EGFR mutations, and compares the prevalence of mutations in smokers and non-smokers. It also goes over new approaches such as liquid biopsies, fourth-generation inhibitors, and therapies that utilize AI. In order to improve the future outlook of NSCLC patients, our work connects molecular understanding of knowledge with clinical development.