Clinical Features, Molecular Biology, and the Metastatic Microenvironment in Lung Cancer Brain Metastases: Implications for Treatment Decisions

Abstract Brain metastases (BM) represent a highly aggressive, clinically distinct subtype of lung cancer, often associated with poor prognosis. Historically, treatment options for BM have been limited and largely nonspecific. However, recent advancements in clinical and preclinical research have led to substantial improvements in patient outcomes. This review focuses on BM arising from lung cancer, providing an overview of recent findings related to clinical characteristics, diagnostic strategies, and early metastatic processes. Multi‐omics analyses have elucidated the molecular mechanisms underlying tumor initiation and progression, with particular emphasis on the role of the tumor microenvironment. In this review, preclinical BM models, detailed signaling pathways, and emerging clinical therapies are also discussed. Current treatment approaches are multidisciplinary, and multi‐omics technologies enhance both diagnosis and therapeutic strategies by revealing the complex biology of BM. Continued research is needed to identify BM‐specific drug targets, particularly those involved in crossing the blood–brain barrier and remodeling the brain microenvironment. Addressing these challenges is crucial for improving clinical outcomes in patients with BM.