Advances in the Molecular Landscape of Lung Cancer Brain Metastasis

SIMPLE SUMMARY: Patients with lung cancer have high rates of brain metastasis (BM). Despite available therapies, patient prognosis is poor. Studies have shown genetic alterations associated with the metastatic spread of lung cancer cells. However, the precise mechanisms governing BM are still unclear. In this review, we comprehensively describe the major steps of metastatic spread of lung cancer to the brain, addressing the influence of the tumor microenvironment and the molecular determinants of progression. Furthermore, we highlight the advances in the molecular diagnostics of BM by liquid biopsies and discuss novel treatment strategies. ABSTRACT: Lung cancer is one of the most frequent tumors that metastasize to the brain. Brain metastasis (BM) is common in advanced cases, being the major cause of patient morbidity and mortality. BMs are thought to arise via the seeding of circulating tumor cells into the brain microvasculature. In brain tissue, the interaction with immune cells promotes a microenvironment favorable to the growth of cancer cells. Despite multimodal treatments and advances in systemic therapies, lung cancer patients still have poor prognoses. Therefore, there is an urgent need to identify the molecular drivers of BM and clinically applicable biomarkers in order to improve disease outcomes and patient survival. The goal of this review is to summarize the current state of knowledge on the mechanisms of the metastatic spread of lung cancer to the brain and how the metastatic spread is influenced by the brain microenvironment, and to elucidate the molecular determinants of brain metastasis regarding the role of genomic and transcriptomic changes, including coding and non-coding RNAs. We also present an overview of the current therapeutics and novel treatment strategies for patients diagnosed with BM from NSCLC.