The concept of using liquid biopsies to examine the genetic profile of tumors was first described in 1948 by Mandel and Metais. However, this topic did not receive much attention until recently due to the advances in molecular techniques coupled with the advent of molecularly targeted therapies for treating various types of cancers. Although the mechanism(s) through which tumor cells shed their genetic material into the systemic circulation is not fully understood, this process can be broadly categorized into passive and active mechanisms. Without delving into the intricacies of each process, passive mechanisms generally involve the release of tumor DNA into the circulation after cell necrosis or apoptosis, whereas in the latter, the tumor spontaneously sheds fragments of its DNA into the blood stream to affect the transformation of susceptible cells at distant sites.
The two main approaches that are currently pursued to detect tumor DNA in the blood include analyzing cfDNA and detecting CTCs. Of note, recent studies suggest that tumors eject small vesicles also referred to as exosomes, which may also be used to detect tumor DNA; however, this section primarily focuses on the clinical applications of CTCs and cfDNA.
Circulating tumor cells are intact tumor cells that are dislodged into the systemic circulation. These cells serve as seeds for subsequent growth of additional tumors (metastasis) at distant sites. Circulating tumor cells are primarily detected in various metastatic carcinomas such as breast, prostate, lung and colorectal cancers. Given the fact that most CTC isolation platforms necessitate that the blood sample be processed within 96 hours after collection, one of the major pitfalls of this approach is the inability to biobank the collected intact cells. On the other hand, cfDNA are fragments of tumor DNA, around 160 to 180 base pairs in length with a higher prevalence of mutations in the smaller fragments. One of the main advantages of cfDNA is that it can be analyzed from biobanked biological fluids (including frozen plasma or serum).
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