The role of SMARCA4 in lung cancer.

Lung cancer remains one of the leading causes of mortality among cancer patients. Chromatin remodeling is a crucial epigenetic process in cancer, primarily regulated by alterations in genes encoding subunits of the switch/sucrose non-fermentable (SWI/SNF) complex. SMARCA4 and SMARCA2 are two mutually exclusive catalytic subunits within the SWI/SNF complex responsible for utilizing ATP hydrolysis to provide energy for chromatin remodeling. In lung cancer, SMARCA4 is one of the most common mutated subunits of the SWI/SNF complex. Patients with SMARCA4-deficient lung cancer typically experience poorer clinical outcomes. At present, there is no established targeted therapy designed specifically for this type of cancer. Here, we mainly discuss the mechanisms of SMARCA4 in lung cancer development and progression, its co-mutations and mutually exclusive mutations, cellular origin, clinical pathological characteristics, diagnosis and treatment of SMARCA4-deficient lung cancer. We also investigate the concept of synthetic lethality between SMARCA4 and SMARCA2, along with susceptibility to SMARCA4-deficient lung cancer and potential applications of immunotherapy.