2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03G.03 Role of SMARCA4, Core SWI/SNF Complex Component, in Small Cell Lung Cancer Development

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This study investigates the role of the SMARCA4 gene in small cell lung cancer (SCLC). SCLC is a highly aggressive cancer characterized by numerous mutations, including the loss of tumor suppressor genes P53 and RB. SMARCA4 is a key component of the SWI/SNF chromatin modifying complex, which regulates gene transcription. Inactivating mutations in SMARCA4 are commonly found in SCLC tumors.<br /><br />The research explores SMARCA4's tumor suppressor potential, hypothesizing that its deletion would promote tumor growth. Contrary to expectations, deleting Smarca4 in genetically engineered mouse models resulted in decreased tumor development. Notably, SMARCA4-deficient tumors exhibited atypical morphology, losing typical neuroendocrine characteristics associated with SCLC and appearing dedifferentiated. These tumors were more immunogenic, suggesting they might respond better to immunotherapies.<br /><br />In clinical data from SCLC patients, higher SMARCA4 expression was associated with improved overall survival, adding complexity to its role in tumor progression. The findings highlight SMARCA4's critical role in the early stages of SCLC tumorigenesis, suggesting that its alterations drive tumor heterogeneity at different temporal stages.<br /><br />The research team, consisting of experts from the University of Virginia and the National Institutes of Health, underscores the potential of targeting chromatin modifiers like SMARCA4 in developing therapeutic strategies for SCLC, emphasizing its nuanced role in cancer progression. The study is supported by grants from NIH/NCI and NIH/NIGMS.<br /><br />Overall, the study reveals the unexpected necessity of SMARCA4 in early tumor development and its association with tumor phenotype and patient survival, suggesting new avenues for understanding and treating SCLC.

Asset Subtitle

Nicole Kirk

Meta Tag

Speaker Nicole Kirk

Topic Tumor Biology – Translational Biology

Keywords

SMARCA4

small cell lung cancer

SCLC

tumor suppressor

chromatin modifying complex

immunotherapy

tumor heterogeneity

neuroendocrine

gene transcription

therapeutic strategies