The number of publications identified in a Pubmed search for "liquid biopsy" has increased more than ten-fold in just three years (see chart). Dozens of companies have formed in the past five years to develop liquid biopsy tests for cancer. In recent reports, analysts have estimated the liquid biopsy market to be tens of millions of dollars. So why are liquid biopsies now the focus of so much attention?
For years research has focused on gathering the knowledge we need to prevent cancer as much as possible and treat it effectively when it does arise. Now, through all that research, we have gained a deep understanding of the process of carcinogenesis and the associated molecular events, and we are even starting to understand how those molecular events influence the response to various treatments.
But how can we take advantage of all of that knowledge in a clinical setting? That's where liquid biopsies come in. With a liquid biopsy, blood is drawn at the time a clinical decision needs to be made, and the circulating tumor DNA or cells are analyzed. For many patients, a recent tumor tissue biopsy is just not available, but a liquid biopsy can be taken at any time a blood draw is possible.
In the late 1970s, long before liquid biopsy became a buzzword, researchers were beginning to hypothesize that nucleic acids were released from tumor cells, either through an active process or through cell death. Evidence began to grow to suggest that tumor-derived material could indeed be found in the plasma of patients with cancer, and through the 1980s and 1990s, numerous reports were published demonstrating that the same molecular aberrations found in tumors could be found in circulating DNA.
Scientists understood the potential value of this material, but numerous technical hurdles prevented this from being easily translated to the clinic. Circulating tumor DNA is only present in small amounts and is quite fragmented. Furthermore, tumor-derived DNA is only a small portion of the total free DNA in plasma. Small changes in blood collection procedures can have a large effect on the amount of free DNA from healthy cells. So any assay targeting tumor-derived DNA must be sensitive and specific.
In the past ten years, knowledge of the molecular alterations in cancer and development of appropriate technology have both advanced enough to make liquid biopsy assays a reality. Dozens of companies have started to work hard developing liquid biopsy assays, and there has certainly been a lot of hype. The Illumina spin-off Grail drew attention when it was backed by over $100 milllion dollars from Bill Gates, Jeff Bezos, Google, and others. Pathway Genomics' assay was featured on the TV show "Keeping Up with the Kardashians."
But is the hype justified? Many companies are already offering liquid biopsy assays in their own CLIA labs, and data to validate the assays is rapidly being generated. Last spring, Guardant Health presented the results of their assay in 15,000 patients. Furthermore, in April, Epigenomics' Epi proColon became the first circulating tumor DNA-based assay to gain FDA approval. Thus, liquid biopsies will likely become standard of care in the coming years.