Clinical OMICS

MAR-APR 2018

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

Issue link: https://clinicalomics.epubxp.com/i/958440

Contents of this Issue

Navigation

Page 20 of 51

www.clinicalomics.com March/April 2018 Clinical OMICs 19 Imagine an annual physical exam that, along with measuring blood pressure and cholesterol, also screened for mul- tiple cancers with a single blood draw. Several companies, including Grail, Guardant Health, and Freenome have received millions of dollars to finance the development of blood-based screening tests for early cancer detec- tion based on circulating tumor DNA (ctDNA) technology. However, according to Olivier Ele- mento, Ph.D., director of the Caryl and Israel Englander Institute for Precision Medicine at Weill Cornell Medicine, "There is a misconception in the field that [early] detection should be easy… The bottom line is that if you run the numbers it's very unlikely that early detection can be performed with a rea- sonable amount of blood." In a manuscript recently posted on bioRxiv, entitled "Challenges in Using ctDNA to Achieve Early Detection of Cancer," Elemento and co-author Imran Haque, Ph.D., chief scientific officer of Freenome assert that "sta- tistical and physiological limitations suggest that a ctDNA-based muta- tional assay for early detection would be neither commercially nor biologi- cally viable." Firstly, the authors argue that the amount of ctDNA present in the bloodstream—especially for ear- ly-stage cancer and premalignancies— is exceedingly small. In addition, the ctDNA needs to carry a cancer-driving mutation that the screening test recog- nizes, and the extensive heterogeneity in tumors means that not all ctDNA carries the same mutations. Secondly, somatic mutations in normal tissue and blood cells introduce a lot of noise—essentially burying ctDNA signals and decreasing both detection sensitivity and specificity. The manuscript's punchline, said Elemento, is that researchers will need to integrate ctDNA with other signals to develop successful screen- ing platforms. Promising results from CancerSEEK, a multi-analyte, blood- based diagnostic recently published in Science, support the manuscript's argument. "[The authors] realized that if you look at the mutations, you can't detect cancer very accurately. By combining protein level and muta- tions you can achieve better results," said Elemento. However, protein levels are just the tip of the iceberg. DNA methylation, and DNA fragmentation patterns can distinguish between ctDNA and cell- free DNA from normal cells, which could improve detection by increasing the ctDNA signal. Other potentially useful biomarkers include metabolites and miRNA. Elemento also emphasized the importance of longitudinal measure- ments for tracking tumor evolution and preventing over-treatment: "We need to not only have better tests, but also to use those tests as a way to see prospectively the evolution of a disease. If the disease is progress- ing—that's when you would want to intervene."—Meghaan Ferreira Early Cancer Detection via ctDNA May Not Add Up Weill Cornell Medicine's Olivier Elemento, Ph.D. Ca-ssis / Getty Images

Articles in this issue

Links on this page

Archives of this issue

view archives of Clinical OMICS - MAR-APR 2018