A luminescent sensor for investigating serotonin metabolism in neuroendocrine cancer.

Background: Serotonin is emerging as a promising therapeutic target in tryptophan hydroxylase 1-positive tumors, but further mechanistic studies are needed to effectively target dysregulated serotonin metabolism. One challenge is a lack of methods for studying the dynamic nature of serotonin metabolism. Here, we report the development of a genetically encoded luminescent biosensor, termed iSero-Rluc, for the real-time detection of serotonin in live cells.

Inhibition of serotonin biosynthesis in neuroendocrine neoplasm suppresses tumor growth .

Small bowel neuroendocrine tumors (SBNETs) originate from enterochromaffin cells in the intestine which synthesize and secrete serotonin. SBNETs express high levels of tryptophan hydroxylase 1 (Tph1), a key enzyme in serotonin biosynthesis. Patients with high serotonin level may develop carcinoid syndrome, which can be treated with somatostatin analogues and the Tph1 inhibitor telotristat ethyl in severe cases.