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The development of LCBM is shaped by continuous exchange of molecular signals between tumor cells and the brain microenvironment, involving blood\u2013brain barrier remodeling, glial and immune reprogramming, neuronal signaling, and metabolic adaptation. Together, these phenomena support brain colonization, immune escape, and therapeutic resistance. The management of LCBM has improved with the advent of stereotactic radiotherapy, targeted therapy, immunotherapy, chemoimmunotherapy, and antibody\u2013drug conjugates. Yet durable intracranial control is still limited by intrinsic barrier heterogeneity, protected residual intracranial disease, and molecular resistance. This review summarizes recent advances in biology, preclinical modeling, therapeutic resistance, and translational treatment strategies of LCBM. By linking brain\u2010specific metastatic biology with evolving therapeutic approaches, this review provides a framework for understanding LCBM progression and for developing more effective strategies to overcome intracranial resistance.<\/jats:p>","DOI":"10.1111\/cas.70527","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:52:07Z","timestamp":1789098727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies"],"prefix":"10.1111","author":[{"given":"Jun","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Jiangxi Key Laboratory of Neurological Diseases The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangxi Key Laboratory of Neurological Diseases The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangxi Key Laboratory of Neurological Diseases The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangxi Key Laboratory of Neurological Diseases The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Sun Yat\u2010Sen Memorial Hospital  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangxi Key Laboratory of Neurological Diseases The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0605-0955","authenticated-orcid":false,"given":"Meihua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangxi Key Laboratory of Neurological Diseases The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3390\/jcm13237371","article-title":"Lung Cancer With Brain Metastasis\u2010Treatment Strategies and Molecular Characteristics","volume":"13","author":"Wang S.","year":"2024","journal-title":"Journal of Clinical Medicine"},{"key":"e_1_2_17_3_1","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1001\/jama.2025.0560","article-title":"Small Cell Lung Cancer: A Review","volume":"333","author":"Kim S. 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