Clinicians today can analyze a cancer patient’s tumor using a blood sample, a so-called liquid biopsy. But using blood tests to screen seemingly healthy people for early signs of a host of cancers is still a largely hypothetical proposition—and turning that idea into a reality is a much bigger challenge.
Now another company has announced ambitions to pursue blood-based cancer screening. Guardant Health of Redwood City, CA, will release data tomorrow at the American Society of Clinical Oncology conference that could support the idea of using its tests, eventually, to find early cancers in people who have no symptoms.
The key word is “eventually.” Guardant’s liquid biopsies, and those from other companies, already help drug companies find the right cancer patients for clinical trials, and help doctors and patients make treatment decisions. Its test, called Guardant360, hit the market in 2014. The price is $5,800. (Guardant is privately held and does not report sales or revenue figures, but a spokesman said it is “processing” more than 20,000 tests a year.)
In interviews last week, Guardant executives stressed that before they tackle the business of screening the general population, their technology must first prove it can pick up previously undetected cancers in people at high risk for cancer: heavy smokers, for example, or women who have tested positive for BRCA mutations, which are known drivers of some breast and ovarian cancers.
“We’re taking a methodical approach,” said CEO Helmy Eltoukhy. “Once we understand that group we can go to completely asymptomatic patients.”
Through its Guardant360 product, the company already has information from the tumors of more than 20,000 cancer patients, Eltoukhy said, and insights from those data should help detect and identify cancers at a much earlier stage. Eltoukhy likened it to finding ancestors in a family tree of mutations: “Basically we’re working backwards.”
With a new version of its technology that can sequence more deeply from a larger blood sample than before, Guardant is sponsoring studies at academic centers to test high-risk people in five cancers: breast, ovarian, pancreatic, lung, and colorectal. (Guardant calls it the LUNAR program, which is an intentional nod, perhaps a bit tongue-in-cheek, to the two national cancer “moonshot” programs, one led by the Obama administration, one by billionaire Patrick Soon-Shiong.)
Pamela Munster, an oncologist who specializes in BRCA research at the University of California, San Francisco, will run the ovarian study. It will analyze blood samples from BRCA-positive women: 30 with advanced cancer, 30 with early cancer, and 30 with no sign of cancer. Data will be available in a couple years, she said.
Half of the women with BRCA mutations who would otherwise have had their ovaries removed might be able to avoid surgery if a reliable blood test were available, said Munster. A blood test able to reassure a woman that, despite the mutation, no cancer seemed to be present—and therefore removal of the ovaries wasn’t necessary at the moment—would be a breakthrough, said Munster. A BRCA mutation means “you’re sitting on a time bomb,” says Munster, but for women under 40, the risk is still fairly low. “So if you’re 35 and the test tells you to put off the decision, perhaps you can hang onto your ovaries a few more years.”
Liquid biopsies aim to find DNA fragments shed by tumor cells into the blood stream. Proponents say this tumor DNA—referred to as circulating tumor DNA (ctDNA) or cell free DNA—is a far more reliable indicator of cancer than current screening methods, such as the images taken by mammography and lung scans, or the test for prostate-specific antigen (PSA) protein in men’s blood.
“The disease mutations are the pathogenic drivers,” said Eltoukhy. Still, Guardant is proceeding with caution. Researchers in the field note that ctDNA could be the product of dead or dying cells, so it might be giving a skewed picture of a cancer’s strength or composition. And as gee-whiz as sequencing technology has become, fragments of DNA floating in blood—biological needles in a haystack—are still no match for the information contained in intact tumor cells.
Not everyone in the cancer-profiling field is gung-ho for screening. Foundation Medicine (NASDAQ: FMI) of Cambridge, MA, is building a cancer-profiling business using tumor samples, but it recently launched a liquid biopsy product, as well. Is screening next? “We have not expressed interest in the screening market,” said Foundation CEO Michael Pellini. “Our sweet spot is approaching patient care at the time an individual is diagnosed with cancer.”
Pellini said the hurdles to convincing regulators and doctors of the usefulness of screening tests “will likely be extraordinary.” Yet he left a little wiggle room: “There’s real opportunity in the screening market long term, but it’s not our market today.”
Foundation last month filed a patent infringement lawsuit against Guardant, choosing a Texas district court famous for its favoritism toward patent-suit plaintiffs. In initial filings, Foundation did not specify how Guardant was infringing upon its patent. Pellini did not comment on the suit, and Eltoukhy called the suit “meritless.”
Like Foundation, Guardant would argue that screening is not its market today. But it’s mapping its route to get there. Meanwhile, Grail has made pan-cancer screening in the general population its prime objective, with an audacious goal of having products deployed as early as 2019.