Going With the Flow: The Promise and Challenge of Liquid Biopsies.

One of the Cleveland Clinic’s Top Ten Medical Innovations for 2017, the liquid biopsy, can potentially be used to analyze the genetics of tumor cells from blood samples to provide an easier, faster, and comprehensive approach to understanding and treating solid tumors. But what exactly is a liquid biopsy? And can it replace tissue biopsy for detecting solid tumors? The detection of cancer biomarkers in blood is not a new concept. Circulating protein tumor markers such as carcinoembryonic antigen or prostate-specific antigen have been used for decades to assess solid tumor burden. However, many malignancies do not have a reliable protein biomarker, and even for those tumors that do, levels of the protein may be elevated for reasons not related to tumor growth or progression. A more promising alternative that is gaining traction is to evaluate tumor products such as circulating cell-free tumor DNA (ctDNA) and circulating tumor cells (CTCs) that are shed into the blood—or other bodily fluids, such as urine or saliva. Circulating tumor cells were first observed in 1869 in the peripheral circulation of a patient with metastatic cancer (Ashworth TR. Australian Med J. 1869;14:146-147), and ctDNA was first reported in the serum of people with cancer in 1977. One reason it took the liquid biopsy so long to catch on is that CTCs and ctDNA are found in low concentrations in the bloodstream. However, the technology has now developed to the point of sufficient sensitivity and specificity to accurately detect these tumor products. A recent large-scale study reported that ctDNA analysis identified cancer mutations in 85% of all advanced tumors, and the genomic profiles obtained correlated highly with those from solid tumor biopsies. A big advantage of the liquid biopsy is that it can be carried out in a simple, noninvasive way that can allow the tumor to be sampled in serial fashion, providing a more comprehensive view of a patient’s cancer than can be obtained through traditional methods, said Ryan Bruce Corcoran, MD, PhD, of Massachusetts General Hospital, Boston. Corcoran pointed out that while a tumor may lie deep within the body or be positioned in a critical organ, rendering tissue difficult or impossible to obtain, veins are easily accessible. And unlike tumor samples, liquid biopsies can capture how a tumor’s molecular profile evolves over time in response to various pressures, including cancer therapies.