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From odor to oncology: non-canonical odorant receptors in cancer

Oncogene volume 43, pages 304–318 (2024)Cite this article

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Abstract

Odorant receptors, traditionally associated with olfaction as chemoreceptors, have been increasingly recognized for their presence and diverse functions in various non-nasal tissues throughout the body. Beyond their roles in sensory perception, emerging evidence suggests a compelling interplay between odorant receptors and cancer progression as well. Alongside the canonical GPCR odorant receptors, dysregulation of non-canonical odorant receptors such as trace amine-associated receptors (TAARs), formyl peptide receptors (FPRs), and membrane-spanning 4A family (MS4As) has been observed in various cancer types, suggesting their contributions to cancer progression. The roles of these non-canonical chemoreceptors in cancer are complex, with some receptors promoting tumorigenesis and others acting as tumor-suppressing factors upon activation, depending on the cancer type. These findings shed light on the potential of non-canonical odorant receptors as therapeutic targets and prognostic markers in cancer, inviting further exploration to unravel their precise mechanisms of action and implications in cancer biology. In this review, we provide a comprehensive overview of the intricate relationships between these chemoreceptors and various types of cancer, potentially paving the way for innovative odor-based therapeutics. Ultimately, this review discusses the potential development of novel therapeutic strategies targeting these non-canonical chemoreceptors.

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Fig. 1: Sketched representation of the olfactory process and the signal transduction pathways involved in perceiving odors.
Fig. 2: Schematic diagram illustrating the potential roles of non-canonical ORs in cancer progression.
Fig. 3: Potential therapeutic strategies targeting non-canonical ORs.

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Acknowledgements

We thank Thuyvan Luu for their helpful comments and English editing on the manuscript. The present research was supported by the research fund of Dankook University in 2023.

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Authors and Affiliations

  1. Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA

    Sung Jin Park & Paul L. Greer

  2. Department of Biomedical Science and Engineering, Dankook University, Cheonan, 31116, Republic of Korea

    Namgyu Lee

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  1. Sung Jin Park
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  2. Paul L. Greer
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Contributions

Conceptualization, SJP and NL; original draft preparation, SJP; review, PLG; review and editing, NL; visualization, SJP; supervision, NL; funding acquisition, NL. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Namgyu Lee.

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Park, S.J., Greer, P.L. & Lee, N. From odor to oncology: non-canonical odorant receptors in cancer. Oncogene 43, 304–318 (2024). https://doi.org/10.1038/s41388-023-02908-y

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