Year of Publication
Doctor of Philosophy (PhD)
Toxicology and Cancer Biology
Dr. Qiou Wei
Small cell lung cancer (SCLC), which accounts for 10-15% of all lung cancer, is the most malignant type that tends to grow fast and spread in its early stages. The 5-year survival rate remains low at 6% overall. Thus, new therapeutic methods and pharmacological targets for SCLC patients are urgently needed. We present novel data indicating that the synthesis of serotonin is upregulated in SCLC compared to normal bronchial epithelial cells and non-small cell lung cancer. Serotonin signaling plays a critical role in various physiological and pathological processes. However, its contribution to SCLC development has not been well understood. The goal of this study is to investigate the role of serotonin signaling in human SCLC development and to test the hypothesis that disrupting the serotonin axis inhibits cancer growth in vitro and in vivo. Here we demonstrated that elevated serotonin contributes to SCLC development, whereas blocking serotonin receptor, HTR3A, prevents part of the serotonin mitogenic effect. Additionally, inhibition of serotonin synthesis enzyme, TPH1, effectively reduces cell proliferation, induces cell apoptosis, as well as suppresses metastasis in vitro and in vivo. We also reported the SCLC organoids from xenograft tumor and liver metastasis tissue, as well as represented the value of interruption TPH1-serotonin-HTR3A axis in both tumoriods.
Digital Object Identifier (DOI)
Hao, Yanning, "UNDERSTANDING AND TARGETING THE TPH1-SEROTONIN-HTR3A AXIS IN SMALL CELL LUNG CANCER" (2023). Theses and Dissertations--Toxicology and Cancer Biology. 47.
Available for download on Sunday, August 10, 2025