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Blood-brain barrier alterations as an initiator of brain metastasis from lung cancer: a new take on an old story

Cancer Gene Therapy volume 32, pages 809–816 (2025)Cite this article

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Abstract

Lung cancer is the most common primary tumor associated with brain metastases. Currently, the molecular mechanisms underlying the pathogenesis of lung cancer brain metastasis (LCBM) have not been fully elucidated and effective therapeutic strategies for treating this disease are still lacking. The blood-brain barrier (BBB) is a selectively permeable membrane and is crucial in maintaining brain homeostasis. Increasing evidence from clinical and pre-clinical studies indicated that metastatic circulating tumor cells from lung cancer can affect the cellular biology of BBB components, and destruct its integrity as well as function to penetrate the BBB to clone in the brain parenchyma, therein producing malignant secondary tumors. Therefore, in this review, we aim to discuss about the involvement of BBB alterations during the initiation of LCBM and the cellular and molecular mechanisms underlying. A better understanding of these pathophysiological processes may help open avenues to develop new therapeutic strategies to prevent or treat this notorious disease.

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Fig. 1: Schematic illustration of lung cancer brain metastasis.
Fig. 2: BBB-related cellular and molecular alterations during the formation of brain metastasis from lung cancer.

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Funding

This work was supported by grants from National Natural Science Foundation of China (82203035) to Jianxiong Ji.

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  1. These authors contributed equally: Jianfen Wu, Haijian Wu, Fengqi Zhou.

Authors and Affiliations

  1. Department of Cardiothoracic surgery, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, China

    Jianfen Wu

  2. Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Haijian Wu, Fengqi Zhou, Yongjie Wang, Chun Wang & Jianxiong Ji

  3. Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, China

    Chun Wang & Jianxiong Ji

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Contributions

CW and JXJ conceived the study and revised the final manuscript. JFW, HJW and FQZ contributed to literature collection and drafting the manuscript. YJW contributed to reviewing and editing the manuscript. All authors read and approved the final manuscript.

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Correspondence to Chun Wang or Jianxiong Ji.

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Wu, J., Wu, H., Zhou, F. et al. Blood-brain barrier alterations as an initiator of brain metastasis from lung cancer: a new take on an old story. Cancer Gene Ther 32, 809–816 (2025). https://doi.org/10.1038/s41417-025-00916-6

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