Blood-Based Cancer Biomarkers in Liquid Biopsy: A Promising Non-Invasive Alternative to Tissue Biopsy

Abstract

Cancer is one of the greatest threats facing our society, being the second leading cause of death globally. Currents strategies for cancer diagnosis consist of the extraction of a solid tissue from the affected area. This sample enables the study of specific biomarkers and the genetic nature of the tumor. However, the tissue extraction is risky and painful for the patient and in some cases is unavailable in inaccessible tumors. Moreover, a solid biopsy is expensive and time consuming and cannot be applied repeatedly. New alternatives that overcome these drawbacks are rising up nowadays, such as liquid biopsy. A liquid biopsy is the analysis of biomarkers in a non-solid biological tissue, mainly blood, which has remarkable advantages over the traditional method; it has no risk, it is non-invasive and painless, it does not require surgery and reduces cost and diagnosis time. The most studied cancer non-invasive biomarkers are circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. These circulating biomarkers play a key role in the understanding of metastasis and tumorigenesis, which could provide a better insight into the evolution of the tumor dynamics during treatment and disease progression. Improvements in isolation technologies, based on a higher grade of purification of CTCs, exosomes, and ctDNA, will provide a better characterization of biomarkers and give rise to a wide range of clinical applications, such as early detection of diseases, and the prediction of treatment responses due to the discovery of personalized tumor-related biomarkers.

Keywords: biomarkers; cancer; circulant tumor DNA (ctDNA); circulant tumor cells (CTC); liquid biopsy; non-invasive.

Figure 1

Schematic of the origin of cell-free DNA (cfDNA), circulating tumor cells (CTCs), and exosomes in the blood by [12], licensed under CC BY-NC-ND. The final, published version of this article is available at http://www.karger.com/?doi:10.1159/000458736.

Figure 2

Biological and physical approaches of enrichment. Retrieved with permission from [23]. Copyright 2016, Elsevier.

Figure 3

Commonly used extraction procedure for nucleic acids. Prior to circulating tumor nucleic acids (ctNAs) detection, several methods have been utilized in order to properly isolate these biomarkers.

Figure 4

Schematic representation of the formation of exosomes and their respective release to the bloodstream by [78], licensed under CC BY 4.0.