Abstract
Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine produced from the essential amino acid tryptophan. Serotonin’s role as a neurotransmitter in the central nervous system and a motility mediator in the gastrointestinal tract has been well defined, and its function in tumorigenesis in various cancers (gliomas, carcinoids, and carcinomas) is being studied. Many studies have shown a potential stimulatory effect of serotonin on cancer cell proliferation, invasion, dissemination, and tumor angiogenesis. Although the underlying mechanism is complex, it is proposed that serotonin levels in the tumor and its interaction with specific receptor subtypes are associated with disease progression. This review article describes serotonin’s role in cancer pathogenesis and the utility of the serotonin pathway as a potential therapeutic target in cancer treatment. Octreotide, an inhibitor of serotonin release, is used in well-differentiated neuroendocrine cancers, and the tryptophan hydroxylase (TPH) inhibitor, telotristat, is currently being investigated in clinical trials to treat patients with metastatic neuroendocrine tumors and advanced cholangiocarcinoma. Several in vitro studies have shown the anticancer effect of 5-HT receptor antagonists in various cancers such as prostate cancer, breast cancer, urinary bladder, colorectal cancer, carcinoid, and small-cell lung cancer. More in vivo studies are needed to assess serotonin’s role in cancer and its potential use as an anticancer therapeutic target. Serotonin is also being evaluated for its immunoregulatory properties, and studies have shown its potential anti-inflammatory effect. Therefore, it would be of interest to explore the combination of serotonin antagonists with immunotherapy in the future.
Highlights
The name serotonin was derived from the Latin word serum and the Greek word tonic [1]. 5-HT is a monoamine produced from the essential amino acid tryptophan
It is synthesized in two steps catalyzed by the enzymes tryptophan hydroxylase (TPH) and dopa decarboxylase (DDC), TPH being the rate-limiting enzyme
The present review aims to redefine serotonin’s role in cancer pathogenesis and the serotonin pathway’s utility as a potential therapeutic target in cancer treatment
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The mammalian brain and the peripheral sites synthesize serotonin separately as it cannot cross the blood–brain barrier. This is facilitated by the rate-limiting enzyme. The functions of serotonin are broad, diverse, and sometimes opposing These effects of serotonin are mediated through several specific 5-HT receptors. In the CNS, the serotonergic neurons’ cell bodies are located in the brain stem’s nine raphe nuclei. These neurons give rise to broad projections to the forebrain, hindbrain, and spinal cord [4]. This has sparked further research into its potential role at different stages of tumor progression and the utility. We shall shed light on the ongoing clinical trials targeting this pathway
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