P-Loop/αC-Helix Compressing Mutations and Exon 20 Insertions in <em>EGFR</em>-Mutant NSCLC: A Rapidly Evolving Therapeutic Landscape

The authors aim to clarify the therapeutic landscape for non-small cell lung cancer (NSCLC) driven by epidermal growth factor receptor (EGFR) P-loop/αC-helix compressing (PACC) mutations and exon 20 insertions (ex20ins), which exhibit distinct structural characteristics and treatment responses compared to classical EGFR mutations. They review current treatment options, emerging resistance mechanisms, and the efficacy of various tyrosine kinase inhibitors (TKIs), highlighting the potential of new mutant-selective therapies. The findings underscore the need for tailored treatment strategies for these specific EGFR mutation subsets.