The possibility of inventing new technologies in the detection of cancer by applying elements of the canine olfactory apparatus

Abstract

In order to find better tools in the diagnosis of cancer in an earlier and more precise manner, researchers have explored the use of volatile organic compound (VOCs) as a way to detect this disease. Interestingly, the canine olfactory apparatus was observed to detect cancer in two anecdotal reports. After the description of these events, researchers began to study this phenomenon in a structured way in order to assess the ability of canines in detecting cancer-related VOCs. Due to the fact that some of these studies have shown that the canine olfactory apparatus is highly proficient in the detection of cancer-related VOCs, in this article we assess the possibility of constructing a bioelectronic-nose, based on canine olfactory receptors (ORs), for the purpose of diagnosing cancer in a more sensitive, specific, and cost effective manner than what is available nowadays. Furthermore, in order to prove the feasibility and the need of the proposed apparatus, we searched for the following type of articles: all of the studies that have examined, to our knowledge, the ability of dogs in detecting cancer; 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 is necessary to express the canine ORs in heterologous cells; 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; and articles that describe examples of already constructed bioelectronic noses, in order to demonstrate the existence of a technical precedent and thus the plausibility of the proposed device.

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.