Harnessing Volatile Organic Compound Biomarkers for Early Cancer Detection: Molecular to Nanotechnology-based Approaches

Abstract

Early-stage cancer diagnosis is considered a grand challenge, and even though advanced analytical assays have been established through molecular biology techniques, there are still clinical limitations. For example, low concentration of target biomarkers at early stages of cancer, background values from the healthy cells, individual variation, and factors like DNA mutations, remain the limiting factor in early cancer detection. Volatile organic compound (VOC) biomarkers in exhaled breath are produced during cancer cell metabolism, and therefore may present a promising way to diagnose cancer at the early stage since they can be detected both rapidly and non-invasively. However, there are challenges in VOC analysis, especially regarding standardization of sampling, necessity for preconcentration, and cancer-specificity of biomarkers. There are also additional challenges, including the design and development of highly sensitive miniaturized sensors that detect VOC biomarkers at low concentrations with minimum cost efforts. In the present article, we have reviewed the potential impact of VOCs in cancer detection in the context of traditional methods such as liquid biopsies, which are typically employed at advanced stages of cancer progression. Described ultrasensitive technologies such as gas chromatography-mass spectrometry (GC-MS) and electronic noses using a variety of nanomaterials have been considered as technologies for breath-based early cancer detection.