Silicon Valley startup is using gene sequencing to identify in the bloodstream free-floating genetic material shed by tumors
There has been plenty of excitement about the new diagnostic technologies designed to identify circulating tumor cells in blood samples. Now, a well-funded Silicon Valley startup has developed a blood test that it says holds promise for detecting early-stage lung and other cancers.
Though experimental, the screening test—which uses gene sequencing to identify in the bloodstream cancer-signaling genetic material shed by tumors—would be a boon for clinical laboratories and health networks. It also could play a role in advancing precision medicine treatments and drug therapies.
GRAIL, a Menlo Park, Calif., life sciences company, presented its initial findings at the 2018 American Society of Clinical Oncology Annual Meeting in Chicago. Its lung cancer data is part of GRAIL’s ongoing Circulating Cell-Free Genome Atlas (CCGA) study, which aims to enroll 15,000 participants and investigate 20 different types of cancers.
“We’re excited that the initial results for the CCGA study show it is possible to detect early-state lung cancer from blood samples using genome sequencing,” said lead study author Geoffrey Oxnard, MD, Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School, in a Dana-Farber news release.
According to the news release, researchers in this initial analysis explored the ability of three different prototype sequencing assays, each with 98% specificity, to detect lung cancer in blood samples:
- Whole-genome bisulfite sequencing (WGBS) detected 41% of early-stage (stage 1-3A) lung cancers and 89% of late-stage (stage 3B-4) lung cancers;
- Whole-genome sequencing (WGS) detected 38% of early-stage cancers and 87% of late-stage cancers; and,
- Targeted sequencing detected 51% of early-stage cancers and 89% of late-stage cancers.
“The initial results showed that all three assays could detect lung cancer with a low rate of false positives (in which a test indicates a person has cancer when there is no cancer),” the Dana-Farber news release noted.
Identifying Disease Risk Before Symptoms Appear
Screening tests help identify individuals who are not displaying disease symptoms but may be at high risk for developing a disease. GRAIL’s goal is to develop a test with a specificity of 99% or higher. This means no more than one out of 100 people would receive a false-positive.
Otis Brawley, MD, Chief Medical and Scientific Officer at the American Cancer Society, points out that specificity is important when developing a population-based screening test that ultimately would be given to large portions of the general public based on age, medical history, or other factors.
“I am much more concerned about specificity than sensitivity [true positive rate], and [GRAIL] exhibited extremely high specificity,” Brawley told Forbes. “You don’t want a lot of false alarms.”
Some cancer experts have a wait-and-see reaction to GRAIL’s initial results, due in part to the small sample size included in the sub-study. Benjamin Davies, MD, Associate Professor of Urology at the University of Pittsburgh School of Medicine, and an expert on prostate cancer screening, told Forbes the early data was “compelling,” but the number of patients in the study was too small to generate excitement.
Oxnard, however, believes the initial results validate the promise of GRAIL’s blood screening test project.
“I was a skeptic two years ago,” Oxnard, a GRAIL consultant, told Forbes. “I think these data need to put a lot of the skepticism to rest. It can be done. This is proof you can find cancer in the blood, you can find advanced cancer, therefore this has legs. This has a real future. It’s going to be many steps down the line, but this deserves further investigation and should move forward.”
Researchers next plan to verify the initial results in an independent group of 1,000 CCGA participants as part of the same sub-study. They then will attempt to optimize the assays before validating them in a larger data set from CCGA, the Dana-Farber news release explained.
Illumina, a sequencing-technology developer, formed GRAIL in 2016, with participating investments from Bill Gates, Bezos Expeditions and Sutter Hill Ventures. Since then, GRAIL has attracted other high-flying investors, including Amazon, Merck, Johnson and Johnson, and Bristol-Myers Squibb.
Forbes notes that as of 2018 GRAIL has raised $1.6 billion in venture capital and has a $3.2 billion valuation, according to private market data firm Pitchbook. Last year, GRAIL merged with Hong Kong-based Cirina Ltd., a privately held company also focused on the early detection of cancer.
While GRAIL’s projects hold promise, anatomic pathologists and clinical laboratories may be wise to temper their enthusiasm until more research is done.
“We all would like to dream that someday you’d be able to diagnose cancer with a blood test,” Eric Topol, MD, Executive Vice President and Professor of Molecular Medicine at Scripps Research, told Forbes. Topol says he’s “encouraged” by GRAIL’s methodical approach, but warns: “We’re at the earliest stage of that.”
—Andrea Downing Peck