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

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.