OLFACTORY RECEPTORS:
Olfactory receptors (ORs) are specialised proteins that detect volatile chemicals that are common odorants in the environment. Discovered in 1991 by Buck and Axel, these chemicals constitute for the largest gene family in humans with approximately four hundred genes [10]. Most ORs are not exclusively expressed or located in the olfactory sensory neurons, however. They have been found in all other human tissues tested to date, yet they’re poorly understood [11]. ORs are highly expressed in different cancer tissues and thus, has been found to possibly be conceivable when it comes to treating specific types of cancer [11].
ORs being nerve cells are most often directly connected to the brain. The olfactory system simply works by scent molecules being detected and recognized by ORs embedded in the ciliary membrane.
Odour recognition firstly involves the binding of odorant molecules to ORs, where once bound, a biochemical chain reaction occurs in the OR cell, which results in a shift of the cell’s electrical charge [12]. This shift causes the cell to set off electrical impulses that are sent to the brain along axons from the olfactory epithelium, the primary region in which signals are successfully processed at neurological level [13]. When this process reaches a critical level, the receptor cells send more signals to the olfactory bulb (OB), which is the part of the brain that processes odour information [14,15]. The OB is situated in the forebrain and relays the olfactory stimuli to transmit them to the olfactory cortex, where the conscious awareness of a smell takes place, and to the limbic system, which is the part of the brain heavily involved with memory and emotion [11,16-19].
COLORECTAL CANCER:
Colorectal is one of the most pertinent types of cancer amongst humanity. With approximately 1.8 million cases in 2018 alone, according to the WHO, this cancer causes much burden and pain for patients. The symptoms can range from rectal bleeding, to change in bowel habits and anaemia [20]. Colorectal cancer affects the digestive system, and depending on where the primary tumour originated, it can be referred to as bowel cancer, colon cancer, or rectal cancer. This form of cancer typically spreads via the bloodstream and the lymph nodes to other parts of the body, particularly the liver, lungs and the peritoneum, and sometimes even bones, as metastatic or stage IV colorectal cancer. Generally, colorectal cancers have been found to be relatively slow growing however they are still very aggressive.
Colorectal cancer develops through multistage processes, involving accumulation of genetic, epigenetic and environmental factors and alterations [21]. In many cases, colorectal cancer is linked with physical inactivity, excess body weight, and the overconsumption of energy, which is especially prominent in Western countries [22].
In recent years, the investigation on how olfactory receptors are linked to the pathogenesis of colorectal cancer has increased, but it is still very scarce and not in depth. Due to the very diverse nature of many ORs, it appears that many have different and versatile functions. Sailem et al. most recently used AI to find that specific ORs being “turned on” can cause worse colon cancer outcomes [23]. Li et al. found that OR1D2, OR4F15 and OR1A1 also disrupted colorectal cancer cases [24]. Xu et. Al also found that OR8D2 acts as a predictor of recurrence risk and prognosis for colon cancer patients [25]. Some ORs seem to have been slightly more researched than others with their involvement in colorectal cancer, one of them being 0R51B4.
OR51B4 is found to be highly expressed primarily in the colon cancer cell line HCT116, and in native human colon cancer tissues. Weber et al. Found that by stimulating the OR with its ligand, Troenan, cell proliferation and growth were inhibited as well as inducing apoptosis, cell death [26]. Lee et al. seems to further agree and find that the regulation of OR51B4 via Troenan can inhibit cancer in the cells thus may be able to be a possible novel target for colon cancer [27]. As colon cancer is accessible from the lumen, the rectal or oral ingestion of Troenan could be plausible to use for a potential treatment.
OR7C1 is another example of a more commonly studied OR in the involvement of colorectal cancer. It has been found to play a crucial role in the physiology of cancer, initiating cells in the colon as an increased expression of OR7C1 correlates to a higher tumorigenicity [28]. In addition, immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients, thus could also be a viable target for treating colon cancer [29].
CONCLUSION:
Olfactory receptors, their involvement, and their potential to act as targets for treating colon/colorectal cancer, more so than many other types of cancer, seems to be promising as being efficacious. Nevertheless, whether humans would be able to find a way to consciously recognise the scent of specific cancer directly is heavily questionable. ORs have very little research to back up any statements and prospects, particularly to administer clinically as of yet, thus it would need much heavier investigation.
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