LAUSR

O ncologists have dreamed of them for years: noninvasive alternatives to tissue biopsies that can quickly identify tumors by the cells, DNA, or other cell components that they shed into patients’ blood. Now, several promising studies and a wave of prototypes suggest that such tests may be within reach. These new approaches to liquid biopsies, led by methods for detecting circulating tumor DNA, have been generating considerable excitement because of their potential to provide easier, less painful options for early detection; more tailored therapies; and better monitoring and prediction of cancer recurrence in lieu of more expensive imaging scans. That excitement, though, comes with a big caveat. For all the encouraging data from the flood of new panels, several experts agree that most of the tests must significantly improve their performance before they are ready for prime time. “This is the future, but we are not there yet,” says Gonzalo Torga, MD, a postdoctoral research fellow at the Brady Urological Institute at Johns Hopkins School of Medicine in Baltimore, Maryland. One liquid biopsy in development, called CancerSEEK, uses circulating proteins and DNA mutations to detect 8 distinct types of cancer. In a recent study in Science, the blood test correctly identified the disease in approximately 70% of 1005 patients who had already been diagnosed with a stage I, II, or III cancer.1 If it pans out, the test could offer advanced warning for multiple tumors— liver, pancreatic, esophageal, ovarian, and stomach—that currently lack screening tests. Still, although it demonstrated a specificity of more than 99%, CancerSEEK’s sensitivity varied widely, from a high of 98% for ovarian cancer to a low of 33% for breast cancer. Based in Menlo Park, California, GRAIL, a spinoff of sequencing titan Illumina, is trying to develop its own version of a liquid biopsy for early cancer detection. In June 2018, the company reported that combined results from several of its sequencing-based methods rivaled those of CancerSEEK: it correctly diagnosed ovarian, liver, pancreatic, and gallbladder cancer more than 80% of the time, but it was less than 25% accurate in detecting breast cancer. In March 2018, the American Society of Clinical Oncology and the College of American Pathologists released a joint review of 77 articles describing liquid biopsy tests for solid tumors based on circulating tumor DNA analysis.2 Despite the tests’ potential, the expert panel concluded that the majority yielded “insufficient evidence of clinical validity and utility” for advanced cancers and even less evidence for early-stage cancers, treatment monitoring, or detection of residual disease.