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Neurotropism and Therapeutic Targeting of Brain Metastases in Small Cell Lung Cancer.

Triparna Sen·Elisa Gobbini·Khalis Mustafayev·Logan S Spiegelman·Fatma Nihan Akkoc Mustafayev·Fred R Hirsch·Asrar A Alahmadi·Manmeet S Ahluwalia
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Abstract

Small cell lung cancer (SCLC) is an aggressive malignancy marked by rapid progression, early dissemination, and a pronounced propensity for brain metastases (BM), which develop in up to 80% of patients. SCLC is defined by profound genomic instability, lineage plasticity, and rapid drug resistance. The establishment of BM is promoted by neuronal mimicry, enhanced intercellular adhesion, and dynamic cross-talk with astrocytes and microglia. Emerging therapies targeting delta-like ligand 3 and B7H3 have demonstrated encouraging intracranial activity. Despite these advances, treatment resistance and limited brain drug penetration remain major unmet needs. This review highlights recent advances in SCLC BM biology and precision therapeutic strategies.

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HumansBrain NeoplasmsLung NeoplasmsSmall Cell Lung CarcinomaAnimalsJournal ArticleReviewResearch Support, Non-U.S. Gov't

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Triparna Sen, Elisa Gobbini, Khalis Mustafayev, Logan S Spiegelman, Fatma Nihan Akkoc Mustafayev, Fred R Hirsch, Asrar A Alahmadi, Manmeet S Ahluwalia. 2026-09-15. Neurotropism and Therapeutic Targeting of Brain Metastases in Small Cell Lung Cancer.. https://doi.org/10.1158/0008-5472.can-25-5968

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