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Theranostics 2023; 13(3):1109-1129. doi:10.7150/thno.81403 This issue Cite

Review

Exploring neurotransmitters and their receptors for breast cancer prevention and treatment

Ruo Qi Li^1,5, Xiao Hong Zhao^2,5, Qin Zhu¹, Tao Liu³, Hubert Hondermarck², Rick F. Thorne⁴, Xu Dong Zhang^2,4✉, Jin Nan Gao^1✉

1. General Surgery Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, China.
2. School of Biomedical Sciences and Pharmacy, The University of Newcastle, New South Wales, Australia.
3. Children's Cancer Institute Australia for Medical Research, The University of New South Wales, Sydney, NSW, Australia.
4. Translational Research Institute, Henan Provincial and Zhengzhou City Key laboratory of Non-coding RNA and Cancer Metabolism, Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer, Zhengzhou University People's Hospital and Henan Provincial People's Hospital, Academy of Medical Sciences, Zhengzhou University, Henan, China.
5. These authors contributed equally to this work.

✉ Corresponding authors: Jin Nan Gao or Xu Dong Zhang, LS3-49, Life Sciences Building, The University of Newcastle, Callaghan, NSW, Australia. Ph: 61 2 49218906. Fax: 61 2 49217311. Email: sxjinnancom or Xu.Zhangedu.au

Abstract

While psychological factors have long been linked to breast cancer pathogenesis and outcomes, accumulating evidence is revealing how the nervous system contributes to breast cancer development, progression, and treatment resistance. Central to the psychological-neurological nexus are interactions between neurotransmitters and their receptors expressed on breast cancer cells and other types of cells in the tumor microenvironment, which activate various intracellular signaling pathways. Importantly, the manipulation of these interactions is emerging as a potential avenue for breast cancer prevention and treatment. However, an important caveat is that the same neurotransmitter can exert multiple and sometimes opposing effects. In addition, certain neurotransmitters can be produced and secreted by non-neuronal cells including breast cancer cells that similarly activate intracellular signaling upon binding to their receptors. In this review we dissect the evidence for the emerging paradigm linking neurotransmitters and their receptors with breast cancer. Foremost, we explore the intricacies of such neurotransmitter-receptor interactions, including those that impinge on other cellular components of the tumor microenvironment, such as endothelial cells and immune cells. Moreover, we discuss findings where clinical agents used to treat neurological and/or psychological disorders have exhibited preventive/therapeutic effects against breast cancer in either associative or pre-clinical studies. Further, we elaborate on the current progress to identify druggable components of the psychological-neurological nexus that can be exploited for the prevention and treatment of breast cancer as well as other tumor types. We also provide our perspectives regarding future challenges in this field where multidisciplinary cooperation is a paramount requirement.

Keywords: Neurotransmitters, Neurotransmitter receptors, Nerves, Tumor microenvironments, Breast cancer

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