Work

The serotonin axis in cancer: metabolism, epigenetics, and immune regulation

Year: 2026

Type: article

Abstract: The serotonin axis, encompassing the biosynthesis, transport, receptor signaling and metabolism of serotonin, has emerged as a context-dependent regulatory network implicated in cancer biology. Beyond its classical neurotransmitter functions, serotonin modulates tumor progression through receptor-dependent signaling pathways and non-canonical mechanisms such as histone serotonylation, which directly links cellular metabolism to epigenetic regulation. Available evidence suggests that these processes can influence tumor cell proliferation, metabolic adaptation, plasticity and therapeutic drug resistance. Furthermore, the serotonin axis plays a context-dependent role in shaping the tumor microenvironment by regulating the functions of T cells, macrophages and other stromal components, thereby influencing responses to cancer immunotherapy. These diverse regulatory mechanisms have prompted the development of therapeutic strategies targeting serotonin biosynthesis and metabolism, serotonin transport, receptor signaling, and serotonylation, although their efficacy remains highly context-dependent. We further discuss emerging mechanistic insights, unresolved questions, and the opportunities and challenges for developing context-dependent therapeutic strategies targeting this axis.

Source: Molecular Cancer

DOI: 10.1186/s12943-026-02764-w

Authors: Jiazhuang Zhu, Junping Bai, Liwei An, Chunlin Zhang

Institutions: Tongji University, Shanghai Tenth People's Hospital

Language: English

Topic: Cancer, Stress, Anesthesia, and Immune Response

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,090