SMARCA4: Current status and future perspectives in non-small-cell lung cancer

SMARCA4, also known as transcription activator, is an ATP-dependent catalytic subunit of SWI/SNF (SWItch/Sucrose NonFermentable) chromatin-remodeling complexes that participates in the regulation of chromatin structure and gene expression by supplying energy. As a tumor suppressor that has aberrant expression in ∼10% of non-small-cell lung cancers (NSCLCs), SMARCA4 possesses many biological functions, including regulating gene expression, differentiation and transcription. Furthermore, NSCLC patients with SMARCA4 alterations have a weak response to conventional chemotherapy and poor prognosis. Therefore, the mechanisms of SMARCA4 in NSCLC development urgently need to be explored to identify novel biomarkers and precise therapeutic strategies for this subtype. This review systematically describes the biological functions of SMARCA4 and its role in NSCLC development, metastasis, functional epigenetics and potential therapeutic approaches for NSCLCs with SMARCA4 alterations. Additionally, this paper explores the relationship and regulatory mechanisms shared by SMARCA4 and its mutually exclusive catalytic subunit SMARCA2. We aim to provide innovative treatment strategies and improve clinical outcomes for NSCLC patients with SMARCA4 alterations.