The development of liquid biopsies has occurred over the past several years due to advances in the sequencing of the human genome. These advances have made it possible for researchers to detect genetic mutations in cancers. Liquid biopsy assays have resulted from scientific research demonstrating that unique cancer mutations can show up as microscopic fragments of DNA or RNA in a patient's blood. Tumor-related, freely circulating DNA or RNA are released by tumor cells and circulate in the blood of cancer patients.
As early as 1869, Thomas Ashworth first observed circulating tumor cells (CTCs) in a patient with metastasis and suggested that these tumor cells were shed into the bloodstream, leading to metastatic cancer. A long period of time passed before scientists began quantifying cell-free DNA (cfDNA), which describes DNA that is freely circulating in the bloodstream but is not necessarily of tumor origin. In 1948, researchers first detected and quantified cfDNA in both healthy and diseased patients. In 1966, researchers discovered high levels of cfDNA in lupus patients, and in the 1980s, cfDNA was first discovered in oncology patients. Unfortunately, at that time researchers were unable to differentiate between tumor and healthy cfDNA.
It was in 1994 that scientists were able to advance to the point where they could detect specific mutations in cfDNA. In 1997, Dennis Lo was able to detect fetal cfDNA in the blood, and in 2000, Veridex introduced the first commercially available liquid biopsy assay, the CELLSEARCH® CTC test.
In June 2016, the FDA approved the first liquid biopsy test, the cobas® EGFR Mutation Test, as a cfDNA test for the EGFR gene mutation in blood from lung cancer patients. Currently, there continues to be a growing interest in the liquid biopsy assay, including an increasing number of companies involved in the development of these tests for the diagnosis and stratification of cancer patients.