Non-Invasive Liquid Biopsies Become a Reality in Today’s Personalized Cancer Treatment

Cancer is a complex, heterogeneous disease presenting a worldwide health problem in industrialized and developing nations alike. Treatment has generally relied upon the analysis of primary tumor specimens for the comprehensive characterization to help develop and guide personalized treatment. But due to the heterogeneity of the tumor cell population, sampling error can lead to incomplete and insufficient information regarding the actual complete tumor biology, which can lead to inadequate treatment. As cancer progresses and becomes refractory to treatment, clinicians can no longer rely solely on the primary tumor to guide next treatment steps, as the biology driving these resistant cells is clearly different from that in its primary stage. Cancer is indeed a constantly evolving and dynamic process and developing a means to detect any such changes to better inform clinical decisions is paramount to achieving the best possible outcomes. Over the past decade investigations have been made into isolating of cancer biomarkers and evaluating cancer related mutations using physiological biofluids and the answers to achieve better clinical treatments are hidden in the bloodstream where minimally invasive tests, known as “liquid biopsies”, [1,2] hold great promise for personalized cancer treatment. In addition to blood, liquid biopsies of other body fluids such as urine, saliva, and Cerebrospinal Fluid (CSF) have been shown to contain tumor-derived genetic materials [3,4]. Much of the early liquid biopsy studies have been in lung, breast and prostate cancers but this technology is anticipated to have an impact on all types of cancer. In the last few years, liquid biopsies have gained significant attention and the technologies applied in liquid biopsy research have been extensively reviewed. A number of circulating biomarkers can be isolated from liquid biopsies. In particular, circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) also known as circulating tumor DNAs (ctDNAs) are the two main types of potential blood-based biomarkers; alongside microRNAs (miRNAs), exosomes and micro vesicles [5]. To monitor the real-time dynamics of cancer the presence of DNA mutations, epigenetic alterations and other tumor specific abnormalities such as Microsatellite Instability (MSI) and Loss of Heterozygosity (LOH) have diagnostic value. In this context, the ability to detect ctDNA fragments in a patient’s plasma that have been shed from any tumor, has enabled clinicians to repeatedly and non-invasively interrogate the dynamic evolution of human cancers and the plasma