PIK3CA mutation as an acquired resistance driver to EGFR-TKIs in non-small cell lung cancer: Clinical challenges and opportunities

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have significantly enhanced the treatment outcomes in non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, the occurrence of acquired resistance to EGFR-TKIs is an unavoidable outcome observed in these patients. Disruption of the PI3K/AKT/mTOR signaling pathway can contribute to the emergence of resistance to EGFR TKIs in lung cancer. The emergence of PIK3CA mutations following treatment with EGFR-TKIs can lead to resistance against EGFR-TKIs. This review provides an overview of the current perspectives regarding the involvement of PI3K/ AKT/mTOR signaling in the development of lung cancer. Furthermore, we outline the state-of-the-art therapeutic strategies targeting the PI3K/AKT/mTOR signaling pathway in lung cancer. We highlight the role of PIK3CA mutation as an acquired resistance mechanism against EGFR-TKIs in EGFR-mutant NSCLC. Crucially, we explore therapeutic strategies targeting PIK3CA-mediated resistance to EGFR TKIs in lung cancer, aiming to optimize the effectiveness of treatment.