The possibility of inventing new technologies in the detection of cancer by applying elements of the canine olfactory apparatus
Introduction
In medicine, the odor of patients has been a great tool in the diagnosis of some diseases. For example, it is known that ancient Greeks were the first to harness the odor of patients and their corporal fluids as a way to diagnose certain pathologies [1]. Based on this ancestral knowledge, in the last decades scientists have been searching more precise and less invasive ways for the detection of several diseases. Therefore, the research to detect and identify some volatile organic compounds (VOCs), which are a source of odors, as a way to develop new diagnostic methods, has been of great importance to medical sciences [2], [3], [4]. VOCs are molecules capable of volatilizing at room temperature and are the product of different metabolic pathways [5], [6]. The National Aeronautics and Space Administration along with the Jet Propulsion Laboratory and Caltech were one of the pioneers in the development of a sensor that could detect these volatile organic compounds [7], [8]. Furthermore, Krishna Persaud was one of the first individuals that proposed the utilization of these sensors in order to detect certain disease processes [9], [10], [11].
In cancerous cells, a change in the rate of oxidative stress, lipid peroxidation, and gene sequences leads to abnormalities in the biochemical pathways of these cells and thus to the production of specific VOCs [12]. Based on the last information published by GLOBOCAN in 2008, the cancer types with the highest incidence are breast cancer (10.9%), prostate cancer (PCa) (7.1%), lung cancer (LC) (12.7%) and colorectal cancer (9.8%), while the cancer types with the largest mortality are LC (18.2%), stomach cancer (9.7%), liver cancer (9.2%) and colorectal cancer (8.1%) [13].
In an effort to diagnose this disease in earlier stages and thus to reduce its mortality, several diagnostic tests have been used. Nevertheless, in the detection of cancer these tests present several drawbacks. For example, mammography in women ages 40–49 has a lower sensitivity and specificity when compared with older women [14]; in LC low dose spiral CT scan has not been able to reduce mortality in patients who are affected by this disease [15]. Moreover, because the current algorithms and diagnostic methods in the diagnosis of LC are not very precise most patients are diagnosed in late stages of this disease and less than 20% of diagnosed individuals are eligible for curative surgery [16].
To increase the likelihood of detecting cancer in earlier stages, with a greater specificity, sensitivity, and efficiency to what is already mentioned in the literature, and due to the ability of dogs to detect cancer-related VOCs; we assess the possibility of inventing a bioelectronic nose (a combination of a biological recognition part, olfactory receptors (OR), and a non-biological sensing platform) based on the canine olfactory apparatus [5], [6], [17], [18], [19], [20], [21], [22], [23], [24], [25].
In order to prove the feasibility of the proposed bioelectronic nose, we searched throughout the literature for the following type of articles: (1) all or most of the articles that have assessed the ability of dogs in detecting cancer, so as to evaluate if this skill portrayed by canines is good enough in order to translate it into a bioelectronic nose. (2) Articles that assess the dog olfactory receptor (OR) gene repertoire, since a central part of the proposed bioelectronic nose is being able to recognize the odorant that emanates from the cancerous lesion; and for that purpose we consider that is necessary to express in heterologous cells the canine olfactory receptors that are responsible for detecting the cancer-related VOCs. In order to achieve such purpose is essential to know and understand the dog OR repertoire. (3) Examples of articles that depict different devices that have been built for the purpose of detecting cancer-related VOCs, so as to assess if the construction of the proposed apparatus is needed. (4) Articles that describe examples of already constructed bioelectronic noses, which have used ORs expressed in heterologous cells as the biological sensing element of the apparatus, in order to demonstrate the existence of a technical precedent and thus the plausibility of the proposed device.
Section snippets
Canine clinical findings
The observation that dogs are proficient in smelling cancer was perceived by Sir Hywel Williams and Andres Pembroke. In a letter to The Lancet they reported that one of their patients sought a consultation with them due to the great interest that her dog showed in a skin lesion on one of her legs. It was later excised, analyzed and proven to be a malignant melanoma. Years later, it was published that another patient was diagnosed with skin cancer, this time basal cell carcinoma, when he sought
Evaluation of the hypothesis
Some of the mentioned studies that assessed the ability of dogs in detecting cancer-related VOCs are not very promising in their results, while some achieved very favorable results. Moreover, as noted on Table 1 all of them have some flaws in their methodologies. Nevertheless, we believe that they prove that some canines have the innate ability of detecting cancer in a highly prolific manner, even in its early stages. Furthermore, the previous statement can be corroborated by the already
Conclusion
In light of the given information and with the right team of researchers (encompassing for example, physical engineers, electronic engineers, and geneticists), we consider that the realization of a bioelectronic nose for the detection of cancer (through the breath, urine, or blood from patients), based on of the canine olfactory apparatus is a realistic possibility. Furthermore, we envision an apparatus were the electronic component and the biological one (the nanovesicles) would be sold
Conflict of interest
The authors declare that there is no conflict of interest.
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2022, Applied Animal Behaviour ScienceCitation Excerpt :Several reviews have previously summarized portions of this field but are relatively narrow in scope. Jezierski et al. (2015) and (Pomerantz et al., 2015) published reviews focused on the utilization of canine olfaction to detect cancer in humans. These works provided valuable insight into the methodological characteristics of detection studies, but excluded those in which dogs were trained to detect diseases other than cancer, or to detect disease in organisms other than humans.
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2020, Medical HypothesesCitation Excerpt :Besides the unknown nature of the cancer-related compounds there is so far no consensus on the equivalence of the different analytical approaches. Likewise, the repeatedly reported detection of lung and other cancers in breath and urine of patients by sniffer dogs [32-39] remains completely unresolved with regards to the responsible volatile compounds. From the current literature, it appears that there is little progress to be expected beyond the current state of understanding with breath-based approaches.
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2018, Journal of Thoracic OncologyCitation Excerpt :However, the ability of trained dogs to detect lung cancer–related scent patterns represented a novel concept which links canine scent detection to pattern recognition–based models of the currently available e-nose devices.13 In addition, the use of canine olfactory receptors as a biophysical template to structure e-noses is being investigated (see below).14 The exhaled breath can be analyzed based on two distinct albeit complementary approaches (Fig. 2)15: (1) VOC identification, and (2) VOC patterning.
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