| |
'Liquid biopsy' for cancer promises early detection
|
| |
| |
Download the PDF here
Science 19 Jan 2018, see below
--------------------------------
18 January 2018
Simple blood test detects eight different kinds of cancer
Nature
'Liquid biopsy' technique looks for genetic mutations and proteins linked with tumors.
A single blood test could one day be used to detect a variety of cancers, results from a preliminary trial suggest.
The past few years have seen a bevy of experimental tests called liquid biopsies that hold the promise of detecting and tracking tumours from a simple blood draw. Many of these tests are designed to detect a single kind of cancer by spotting tumour-associated mutations in DNA sequences found floating freely in the blood.
The latest study, published on 18 January in Science1, is unusual in that it tests not only for these DNA mutations, but also for aberrant levels of certain proteins, in an effort to detect eight different cancers. The test was able to detect disease in about 70% of more than 1,000 people who had already been diagnosed with cancer.
The researchers hope that their work could eventually lead to a test that is simpler and cheaper than the intensive sequencing involved in some other liquid biopsies. "They end up with performance that is similar to other approaches, but with what looks to be a much more cost-effective approach," says Nitzan Rosenfeld, a cancer researcher at the University of Cambridge, UK.
Needle in a haystack
Many groups in academia and industry have focused on using liquid biopsies to track cancer progression and to guide physicians as they formulate a treatment plan.
But oncologist Nickolas Papadopoulos at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, and his colleagues wanted to develop a test that could detect cancers early, when they are easier to treat.
Such tests are particularly challenging: small tumours don't usually release as much DNA into the bloodstream as larger tumours. And false positives are a concern for tests that are intended to be administered to large populations of healthy individuals — an incorrect result can cause people undue stress and lead to unnecessary and potentially harmful treatments.
The researchers looked for ways to make their liquid biopsy more sensitive without also raising the risk of a false-positive result. The test they developed — dubbed CancerSEEK — examines the levels of 8 proteins and the presence of mutations in 16 genes.
The team tested the liquid biopsy on people who had already been diagnosed with one of eight cancers: ovarian, liver, stomach, pancreatic, esophageal, colorectal, lung or breast. And they excluded individuals whose cancer had spread to other parts of the body, so they could focus on early stages of the disease.
The effectiveness of CancerSEEK varied widely depending on the cancer: it detected 98% of ovarian cancers, but only 33% of breast cancer cases1. It was able to pinpoint the organ in which the disease had taken root in about 63% of patients. But the test performed better on later-stage cancers than on earlier ones, finding 78% of stage III disease versus 43% of stage I tumours.
Seeking sensitivity
Even so, those numbers are high enough to warrant further studies, says Rosenfeld, who is also chief scientific officer at the liquid-biopsy company Inivata in Cambridge. "Even if you only catch half of the cancers, that's great." What's unclear, however, is whether CancerSEEK is able to detect undiagnosed cancers, Rosenfeld adds.
Another concern is whether the false-positive rate might be higher in the general population, says Catherine Alix-Panabieres, a cancer researcher at the University of Montpellier in France. Some seemingly healthy people could harbour inflammatory diseases that alter the levels of the proteins targeted by the test, she says.
It could take years to address those concerns. But researchers have already begun a study that will test CancerSEEK in at least 10,000 healthy individuals, says Papadopoulos, who has served as an adviser to a liquid-biopsy company called Personal Genome Diagnostics in Baltimore. Researchers plan to follow those participants for five years.
In the meantime, expect to see other teams refine their liquid biopsies by combining DNA sequencing with other blood tests, says Alberto Bardelli, a cancer researcher at the Candiolo Cancer Institute in Turin, Italy. "This paper is provocative," he says. "It points to the fact that we should stop looking at a little part of the picture. Instead, we need to see all of the sources of information in the blood."
---------------------------------
'Liquid biopsy' for cancer promises early detection
Science 19 Jan 2018
Summary
A team of researchers has taken a major step toward one of the hottest goals in cancer research: a blood test that can detect tumors early. Their new test, which examines cancer-related DNA and proteins in the blood, yielded a positive result about 70% of the time across eight common cancer types in 1005 patients whose tumors had not yet spread—among the best performances yet for a universal cancer blood test. It also narrowed down the form of cancer. The work, reported online today in Science, could one day lead to a tool for routinely screening people and catching tumors before they cause symptoms, when chances are best for a cure.
A team of researchers has taken a major step toward one of the hottest goals in cancer research: a blood test that can detect tumors early. Their new test, which examines cancer-related DNA and proteins in the blood, yielded a positive result about 70% of the time across eight common cancer types in more than 1000 patients whose tumors had not yet spread—among the best performances yet for a universal cancer blood test. It also narrowed down the form of cancer, which previously published pan-cancer blood tests have not.
The work, reported online today in Science, could one day lead to a tool for routinely screening people and catching tumors before they cause symptoms, when chances are best for a cure. Other groups, among them startups with more than $1 billion in funding, are already pursuing that prospect. The new result could put the team, led by Nickolas Papadopoulos, Bert Vogelstein, and others at Johns Hopkins University in Baltimore, Maryland, among the front-runners.
"The clever part is to couple DNA with proteins," says cancer researcher Alberto Bardelli of the University of Turin in Italy, who was not involved in the work. The researchers have already begun a large study to see whether the test can pick up tumors in seemingly cancer-free women.
Genetic mutations drive the growth of cancer cells, and dying cells shed some of this mutated DNA into the blood. The Johns Hopkins group and others have shown that so-called liquid biopsies of blood-borne tumor DNA can reveal, for example, whether a patient's cancer should respond to a specific drug. But detecting the scant DNA released by early stage tumors is still challenging. Companies such as the $1 billion Grail, launched in 2016 by sequencing giant Illumina, are using a big data approach, sequencing hundreds of genes in thousands of cancer patients' blood in search of a definitive set of DNA markers.
The Johns Hopkins researchers and collaborators found that gains in the detection rate tailed off when they added more genes to their test. They decided to sequence parts of just 16 genes often mutated in different types of cancer. They then added eight known protein biomarkers characteristic of specific kinds of cancer. This bumped up sensitivity and allowed the team to home in on the tissue type of the tumor.
In blood samples from 1005 patients with eight types of tumors that had evidently not yet metastasized, the test detected between 33% and 98% of cases, depending on the tumor type (see graph, below). The sensitivity was 69% or higher for ovarian, liver, stomach, pancreatic, and esophageal cancers—all types that are difficult to detect early.
The test rarely found cancer that wasn't there. Only seven of 812, or less than 1%, of healthy controls tested positive. And the test, called CancerSEEK, narrowed the origin of the cancer to two possible sites in about 80% of patients. The team, which is applying for patents on CancerSEEK, estimates the cost at less than $500 per sample. "That's a very attractive number," says molecular pathologist Anirban Maitra of the MD Anderson Cancer Center in Houston, Texas, because it is in the range of other cancer screening tests such as colonoscopy.
Maitra and others point to caveats, however. One is that the cancer-related proteins used by the test reflect tissue damage and can also appear in people with inflammatory diseases such as arthritis. That means the 1% false positive rate will likely be higher in less healthy populations, notes proteomics researcher Lance Liotta of George Mason University in Manassas, Virginia. What's more, the 1005 patients already had cancer symptoms; CancerSEEK probably won't work as well in asymptomatic patients whose smaller tumors may shed less DNA. In fact, the test picked up only 43% of very early, stage 1 cancers. "We're still not there yet," Bardelli says.
The Johns Hopkins team thinks CancerSEEK is ready for testing as a screening tool. "A test does not have to be perfect to be useful," Papadopoulos says. In collaboration with Johns Hopkins, the Geisinger Health System in Pennsylvania has already begun to use CancerSEEK on blood samples from female volunteers between ages 65 and 75 who have never had cancer. The planned $50 million, 5-year study of up to 50,000 women is being funded by a private philanthropic group, The Marcus Foundation.
For those who test positive twice, the next step will be imaging to find the tumor. But that will bring up questions raised by other screening tests. Will the test pick up small tumors that would never grow large enough to cause problems yet will be treated anyway, at unnecessary cost, risk, and anxiety to the patient? Papadopoulos thinks the problem is manageable because an expert team will assess each case. "The issue is not overdiagnosis, but overtreatment," he says.
Still, others working on liquid biopsies say that it will take time to figure out whether widespread screening of healthy people with a universal blood test can reduce cancer deaths without doing harm. "If people expect to suddenly catch all cancers, they'll be disappointed," says cancer researcher Nitzan Rosenfeld of the University of Cambridge in the United Kingdom. "This is exciting progress," he says. "But evaluating it in the real world will be a long process."
|
|
| |
| |
|
|
|
