Rare oncogenic alterations in NSCLC—focus on atypical EGFR mutations

Summary In non-small cell lung cancer (NSCLC), mutations within the epidermal growth factor receptor (EGFR) gene are very common driver mutations. EGFR tyrosine kinase inhibitors (TKIs), have shown remarkable efficacy in patients with common classical EGFR mutations (L858R and exon 19 deletions). However, the landscape becomes intricate with atypical (also known as uncommon) EGFR mutations, comprising up to 30% of cases. This brief review provides an insight into recent studies, shedding light on the challenges and opportunities posed by uncommon mutations. The exploration encompasses clinical outcomes, treatment responses, and innovative approaches such as structure-based classifications, offering insights into the evolving paradigm of precision medicine for NSCLC patients with diverse EGFR mutations.