ARID1A mutations in lung cancer: biology, prognostic role, and therapeutic implications

AT-interacting domain-rich protein 1A (ARID1A) gene functions as a tumor suppressor gene and is mutated in about 5–10% of lung cancers, mainly as loss-of-function (LOF) alterations.ARID1A deletion is closely related to many clinical features of lung cancer and is an independent predictor of poor prognosis in non-small cell lung cancer (NSCLC).Co-mutations of ARID1A and epidermal growth factor receptor (EGFR) limit the effectiveness of EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy; however, ARID1A deletion may serve as a predictive biomarker for positive response to ICI treatment in lung cancer patients.Mutations in the ARID1A gene regulate PI3K/AKT/mTOR signaling and are involved in cell cycle regulation, metabolic reprogramming, and epithelial–mesenchymal transition.Although ARID1A mutations cannot be directly targeted, their biological effects provide several potential treatment approaches. Mutations in the AT-interacting domain-rich protein 1A (ARID1A) gene, a critical component of the switch/sucrose nonfermentable (SWI/SNF) complex, are frequently found in most human cancers. Approximately 5–10% of lung cancers carry ARID1A mutations. ARID1A loss in lung cancer correlates with clinicopathological features and poor prognosis. Co-mutation of ARID1A and epidermal growth factor receptor (EGFR) results in the limited efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) but increases the clinical benefit of immune checkpoint inhibitors (ICIs). ARID1A gene mutation plays a role in cell cycle regulation, metabolic reprogramming, and epithelial–mesenchymal transition. We present the first comprehensive review of the relationship between ARID1A gene mutations and lung cancer and discuss the potential of ARID1A as a new molecular target.