Synergistic effects and molecular mechanisms of pirfenidone combined with EGFR-TKIs in non-small cell lung cancer

Background

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality globally. While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as osimertinib (OS) and afatinib (AF), have markedly improved clinical outcomes, their efficacy is significantly hindered by the development of acquired resistance. Emerging evidence suggests that p38γ is involved in the progression of NSCLC and the emergence of resistance to EGFR-TKIs. However, whether the p38γ inhibitor pirfenidone (PFD) can enhance the sensitivity of NSCLC to EGFR-TKIs remains unclear. This study aims to evaluate the synergistic antitumor effects of PFD in combination with OS or AF and to elucidate the underlying molecular mechanisms.