Assessment, origin, and implementation of breath volatile cancer markers

Abstract

A new non-invasive and potentially inexpensive frontier in the diagnosis of cancer relies on the detection of volatile organic compounds (VOCs) in exhaled breath samples. Breath can be sampled and analyzed in real-time, leading to fascinating and cost-effective clinical diagnostic procedures. Nevertheless, breath analysis is a very young field of research and faces challenges, mainly because the biochemical mechanisms behind the cancer-related VOCs are largely unknown. In this review, we present a list of 115 validated cancer-related VOCs published in the literature during the past decade, and classify them with respect to their "fat-to-blood" and "blood-to-air" partition coefficients. These partition coefficients provide an estimation of the relative concentrations of VOCs in alveolar breath, in blood and in the fat compartments of the human body. Additionally, we try to clarify controversial issues concerning possible experimental malpractice in the field, and propose ways to translate the basic science results as well as the mechanistic understanding to tools (sensors) that could serve as point-of-care diagnostics of cancer. We end this review with a conclusion and a future perspective.

Real-time monitoring of respiratory absorption factors of volatile organic compounds in ambient air by proton transfer reaction time-of-flight mass spectrometry

“…As many factors, including the exposure concentrations and durations, physiological and metabolic differences of individuals, types of breath samples (mixed exhaled air or alveolar air), sampling and analytical methods [27,[101][102][103], could affect the respiratory AFs, it is difficult to determine whether the differences in AFs between studies were due to differences in subjects, test methods or exposure concentrations (much lower in this study than in the previous studies). However, the AFs observed in this study under low-level BTEX exposure were comparable with most of those conducted under unbelievably high BTEX exposure concentrations, suggesting that initial exposure concentration might not be a critical factor to the AFs considering that the possible errors might also be brought by variability in individual subjects and test methods.…”

Exhaled Gas Detection for Medical Diagnosis: Can it be Made a Tool for Self-Screening?

“…During oxidative stress, ROS and free radicals are excreted from the mitochondria in the cell, generating volatile alkanes. Alternate hypotheses were also proposed to explain the biochemical origin of exhaled breath VOCs and their link with cancer [2,9]. More than 3000 VOCs have been reported to be related to different types of cancers [2,10].…”

“…For example, the VOC concentrations in the body are altered, or new VOCs are generated, to adjust the body's chemistry when it has metabolic diseases like cancer [2]. Oxidative stress and induction of cytochrome p-450 are considered two vital risk factors for cancer development.…”

“…The dogs are attracted either by a change in the strength of the odor or a new odor that the disease creates within the body and then releases. A number of studies relate volatile organic compounds (VOCs) released from the human body to the presence of different kinds to cancers [2,3]. There are now companies that train dogs to sniff out certain specific types of cancers [4].…”

Precursors for cytochrome P450 profiling breath tests from an in silico screening approach

“…This is of great importance in the activation and elimination of (pro-) drugs. Moreover, CYP activity is reflected in specific individual chemical profiles of exhaled breath [4,5].…”