Brain metastasis from lung cancer is a prevalent mode of treatment failure associated with a poor prognosis. The incidence of brain metastasis has recently shown a dramatic increase. The early detection and risk stratification of lung cancer–related brain metastasis would be highly advantageous for patients. However, our current knowledge and comprehension of the underlying mechanisms driving brain metastasis in lung cancer pose significant challenges. This review summarizes the mechanisms underlying brain metastasis, focusing on the intricate interplay between lung cancer–derived tumor cells and the unique characteristics of the brain, recent advancements in the identification of driver genes, concomitant genes, epigenetic features, including miRNAs and long noncoding RNAs, as well as the molecular characterization of brain metastasis originating from other organs, which may further enhance risk stratification and facilitate precise treatment strategies.

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