2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - ePosters-EP01.02: Genetic Determinants of ASCL1–YAP1 Plasticity in Small Cell Lung Cancer

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The study "Genetic Determinants of Plasticity in Small Cell Lung Cancer" from Northwestern University Feinberg School of Medicine investigates the genetic factors influencing cellular plasticity in Small Cell Lung Cancer (SCLC), a malignancy known for its aggressive nature and poor prognosis. SCLC demonstrates high levels of heterogeneity and rapid recurrence after treatment, often leading to chemoresistant tumors. Cellular plasticity, the ability of cancer cells to switch between different states, is a critical contributor to the chemoresistance observed in SCLC.<br /><br />The research highlights key transcription factors (TFs) like ASCL1 and YAP1 that define distinct cancer cell states—neuroendocrine and non-neuroendocrine/mesenchymal, respectively—and underscores the transitions between these states. Using single-cell data, the study identifies TCF7L2 as an important regulator involved in the transitions between ASCL1 and YAP1 states. TCF7L2 is associated with the Wnt signaling pathway and its downstream targets are involved in cellular processes such as epithelial-to-mesenchymal transition (EMT) and cytoskeletal regulation, which are critical for cancer progression and metastasis.<br /><br />In addition, the study explores the role of the NEDD4L gene in manipulating these cellular transitions and evaluates potential therapeutic approaches to target these genetic determinants. By understanding the molecular interactions and the impact of modulating specific gene expressions, the research aims to develop improved clinical interventions that could modulate intratumoral composition, thereby enhancing treatment responses and patient outcomes in SCLC.<br /><br />The findings suggest that targeting the molecular pathways associated with the identified genetic determinants may offer novel therapeutic avenues to combat resistance and improve survival rates in SCLC patients. The study emphasizes the need for continued investigation into the genetic and epigenetic regulation to better understand and treat SCLC.

Asset Subtitle

Elliot Famili-youth

Keywords

Small Cell Lung Cancer

genetic determinants

cellular plasticity

chemoresistance

transcription factors

ASCL1

YAP1

Wnt signaling pathway

NEDD4L gene

therapeutic approaches