TY - JOUR
T1 - Neurotropism and Therapeutic Targeting of Brain Metastases in Small Cell Lung Cancer
AU - Sen, Triparna
AU - Gobbini, Elisa
AU - Mustafayev, Khalis
AU - Spiegelman, Logan S
AU - Akkoc Mustafayev, Fatma Nihan
AU - Hirsch, Fred R
AU - Alahmadi, Asrar A
AU - Ahluwalia, Manmeet S
PY - 2026/7/9
Y1 - 2026/7/9
N2 - 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 crosstalk with astrocytes and microglia. Emerging therapies targeting DLL3 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.
AB - 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 crosstalk with astrocytes and microglia. Emerging therapies targeting DLL3 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.
U2 - 10.1158/0008-5472.CAN-25-5968
DO - 10.1158/0008-5472.CAN-25-5968
M3 - Article
C2 - 42423390
SN - 0008-5472
JO - Cancer research
JF - Cancer research
ER -