Abstract
Lung cancer remains the tumor with the highest global incidence and mortality rates. Current primary treatment modalities encompass targeted therapy, immunotherapy, and chemotherapy; however, a subset of patients derives no benefit from these interventions. Recently, the HER2-targeting antibody drug Disitamab vedotin (RC48) was approved and introduced primarily for gastric and bladder cancers, with minimal investigation in the field of lung cancer. This study demonstrates that FOXA1 directly binds to the promoter region of HER2, influencing the HER2/PI3K/AKT signaling pathway, which consequently modulates factors that foster lung cancer proliferation and impede apoptosis. Unlike FOXA1, HER2 does not influence the expression of FOXA1. Intriguingly, in lung cancer cells, RC48 not only impacts the HER2/PI3K/AKT pathway but also affects the FOXA1/HER2/PI3K/AKT pathway, thereby exerting a robust antitumor effect. In clinical specimens, heightened expressions of FOXA1 and HER2 correlate positively with clinical progression and poorer prognosis. These findings suggest that FOXA1 may serve as a potential biomarker or therapeutic target in future non-small cell lung cancer (NSCLC) treatments, and ongoing research may position RC48 as a transformative agent in lung cancer therapy.