Chinese Medical Journal article decodes the role of neurotransmitter receptors in cancer progression

As global cancer rates continue to rise, the need to understand cancer beyond its cellular and genetic underpinnings has never been more pressing. This shift has led to the growth of cancer neuroscience, an emerging interdisciplinary field that explores the interplay between the nervous system and tumor biology. Traditionally viewed as a disorder of uncontrolled cellular growth, cancer is now understood to be influenced by neural circuits, neurotransmitters, and their receptors, which shape tumor behavior, progression, and even resistance to therapy. 

In response to this evolving perspective, researchers from the Department of Anesthesiology at Renji Hospital, Shanghai JiaoTong University School of Medicine and The First Affiliated Hospital of Wenzhou Medical University conducted a comprehensive review examining the role of neurotransmitter receptors (NRs) in cancer neuroscience. Neurotransmitter receptors are proteins on cell surfaces that respond to chemical messengers from the nervous system, and they are increasingly being implicated in cancer biology. However, their systemic roles in cancer, particularly through neural signaling pathways remain underexplored. Led by Dr. Weifeng Yu, this review, published in the Chinese Medical Journal on [Date], aimed to bridge this gap by mapping out how NRs influence cancer initiation, progression, and treatment response. 

To achieve this, the authors synthesized evidence from basic research, preclinical models, translational studies, and clinical trials. “In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention,” explains Dr. Yu. “The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, and resistance to drugs.” 

The findings revealed that NRs significantly influence tumor biology through diverse neural signaling networks. For instance, the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, particularly via β-adrenergic receptors (β-ARs), were found to promote tumor growth and metastasis. Other receptor systems such as GABAergic, serotonergic, glutamatergic, and other neuropeptide signaling pathways also play vital roles by modulating pathways like cAMP, EGFR, AKT, MAPK/ERK, PI3K/AKT, JAK/STAT3, and β-catenin. These pathways collectively influence cancer cell proliferation, stemness, and the remodeling of the tumor microenvironment. 

Importantly, the study shows that NRs are not merely passive participants, but also promising therapeutic targets. Several compounds targeting these receptors have shown preclinical success in suppressing tumor growth and enhancing treatment response. For instance, β-blockers (β-AR antagonists) have been shown to inhibit tumor angiogenesis and improve immunotherapy efficacy. Similarly, dopamine receptor antagonists like ONC201 and serotonin receptor inhibitors are being evaluated for their anti-tumor effects. 

Another promising direction discussed in the review is the use of nanoparticle-based and receptor-specific drug delivery systems to improve the precision of NR-targeted therapies. Such systems could increase drug accumulation in tumor tissues while sparing healthy cells—an important step toward more effective and safer treatments. 

The study also supports personalized medicine approaches by advocating for profiling NR expression in tumors. Using techniques like immunohistochemistry and genomics, clinicians could stratify patients based on NR expression patterns and tailor treatments accordingly. This strategy could enhance treatment efficacy and reduce unnecessary side effects. 

Nevertheless, challenges remain due to the complexity and heterogeneity of NR functions across different cancer types. Some NRs may exert tumor-promoting effects in one context while acting as suppressors in another. This variability emphasizes the importance of understanding context-specific NR activity and translating basic science findings into well-designed clinical trials. 

Overall, this review offers a comprehensive exploration of how NRs intersect with cancer neuroscience to shape tumor behavior and therapy response. By elucidating the intricate neural pathways through which NRs operate, the study broadens our understanding of cancer biology and highlights promising avenues for precision oncology. Dr. Yu emphasizes, “As research advances, understanding the detailed mechanisms by which NRs affect immune responses could lead to more effective strategies for overcoming immune evasion in cancer.”  

As this emerging field gains momentum, it promises to unlock breakthrough therapies capable of outsmarting cancer’s complexity and overcoming resistance where others fall short. 

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Reference 
DOI: 10.1097/CM9.0000000000003656