Brain Metastasis of Non-small-cell Lung Cancer

Non-small-cell lung cancer (NSCLC) is the major histological type of lung cancers and is characterized by a high incidence of brain metastasis (BrM), which remains an intractable disease. BrM is a multi-step and complex biological process. The formation and outgrowth of BrM involve co-evolution and cross-talk among metastatic cells, immune cells, astrocytes, and the brain microenvironment. To date, patients with NSCLC BrM are treated with multimodal treatments including neurosurgery, radiotherapy, chemotherapy, anti-angiogenic treatment, molecular targeted therapy, and immune checkpoint inhibitors. Nevertheless, the overall prognosis remains dismal, with a median overall survival of <1 year. Understanding the detailed processes and mechanisms of NSCLC BrM including the phenotypic and genotypic heterogeneity of primary lung cancer and matched BrM and the specific immune microenvironment features of BrM would be helpful for developing effective therapeutic strategies. Transforming these novel findings into new treatments and integrating them with paradigms in traditional therapies could improve the overall prognosis of patients with NSCLC BrM. Here, we summarize the epidemiology, known mechanisms, and current systemic treatments for NSCLC BrM. On the basis of recent clinical and translational advances, we discuss the future research directions for NSCLC BrM.