Owlstone Medical and UK’s NHS Study Whether Breath Contains Useful Biomarkers That Could Be Used in Medical Laboratory Tests for Multiple Cancers
Owlstone Medical’s breath biopsy platform takes aim at breath biomarkers for an earlier diagnosis of cancer; could it supplant tissue biopsies sent to pathology labs?
For many years, medical laboratory scientists and pathologists have known that human breath contains molecules and substances that have the potential to be used as biomarkers for detecting different diseases and health conditions. The challenge was always how to create clinical laboratory test technology that could use human breath samples to produce accurate and clinically useful information.
Stated differently, breath, the essence of life, may contain medical laboratory test biomarkers that could provide early-detection advantages to pathology groups in their fight against cancer. Now diagnostics company Owlstone Medical—developer of the Breath Biopsy platform—is about to conduct a clinical study in collaboration with the United Kingdom’s (UK’s) National Health Service (NHS) and others to demonstrate the effectiveness of its breath-based diagnostic tests.
Anatomic pathology groups and clinical laboratory leaders know human breath contains volatile organic compounds (VOCs) that can be useful diagnostic biomarkers for medical laboratory testing. Many possible breath tests have been researched. One such test, the urea breath test for detecting Helicobacter pylori (H. pylori), has been in clinical use for 20 years. As part of the test, patients with suspect stomach ulcers or other gastric concerns, swallow a tablet with urea and exhale carbon dioxide that is measured for H. pylori bacteria.
According to an Owlstone Medical news release, the new study, called the “PAN Cancer Trial for Early Detection of Cancer in Breath,” will explore the ability of Owlstone Medical’s Breath Biopsy platform to detect cancers of the:
Current medical care standards call for these cancers to be diagnosed by analyzing biopsied tissue specimens. If Owlstone Medical’s breath test performs well during trial, it could provide advantages over traditional tissue-based cancer testing that include:
- A non-invasive approach to finding cancer earlier;
- A lower price point as compared to a tissue biopsy cancer test; and
- Faster return of test results, since tissue would not need to be collected from patients during surgical procedures and sent to medical laboratories for analysis.
“By 2030, the number of new cancer cases per year is expected to rise to around 22-million globally. Some cancers are diagnosed very late when there are few treatment options available. Non-invasive detection of cancer in breath could make a real difference to survival,” stated Richard Gilbertson, PhD, Li Ka Shing Chair of Oncology, Director of the CRUK Cambridge Center, and Oncology Department Head at University of Cambridge, in the news release.
How the Breath Biopsy Platform Works
The Breath Biopsy platform relies on Owlstone Medical’s Field Asymmetric Ion Mobility Spectrometry (FAIMS) technology, which the diagnostics company explains is a “fast means to identifying volatile organic compound biomarkers in breath.”
Billy Boyle (above), co-founder and Chief Executive Officer at Owlstone Medical, demonstrates the ReCIVA Breath Sampler. “Positive results from the PAN cancer trial could be game-changing in the fight against cancer,” he noted in the news release. “Success in this study supports our vision of saving 100,000 lives and $1.5 billion in healthcare costs.” This technology has the potential to be disruptive to anatomic pathology, which relies on the analysis of biopsied tissue to detect cancer. (Photo copyright: Owlstone Medical.)
Here is how FAIMS works in the Breast Biopsy platform, according to the Owlstone Medical website:
- Gases are exchanged between circulating blood and inhaled fresh air in the lungs;
- VOC biomarkers in the body’s circulation system pass into air in the lungs, along with oxygen, carbon dioxide, and other gases;
- Exhaled breath contains those biomarkers exiting the body;
- Because it takes one minute for blood to flow around the body, a breath sample during that time makes possible collection and analysis of VOC biomarkers of any part of the body touched by the circulatory system.
One publication compared the capture of VOCs to liquid biopsies, another possible non-invasive cancer diagnostic technique being widely researched.
“The advantage to VOCs is that they can be picked up earlier than signatures searched for in liquid biopsies, meaning cancer can be diagnosed earlier and treated more effectively,” reported Pharmaphorum in its analysis of five technology companies fighting cancer.
As part of the clinical trial, breath samples will be collected in clinic settings with the hand-held Owlstone Medical ReCIVA Breath Sampler (equipped with a dime-sized FAIMS silicon chip). The samples will come from people with a suspected cancer diagnosis who are seeking care at Cambridge University Hospital’s Addenbrooke’s Hospital. To test reliability of the biomarkers, breath samples from patients with cancer and without cancer will be analyzed.
“You’re seeing a convergence of technology now, so we can actually run large-scale clinical studies to get the data to prove odor analysis has real utility,” stated Owlstone Medical co-founder and Chief Executive Officer Billy Boyle, in a New York Times article.
Breath Tests Popular Area for Research
The company’s Breath Biopsy platform is also being tested in a clinical trial for lung cancer being funded by the UK’s NHS. The study involves 3,000 people, the New York Times article reported.
This is not the first time we have reported on Owlstone Medical. A previous e-briefing explored the company’s technology in a study focused on diagnosis of lung cancer (See Dark Daily, “In the UK, Pathologists Are Watching Phase II of a Clinical Trial for a Breathalyzer System That Uses Only a Breath Specimen to Diagnose Lung Cancer,” May 11, 2015.)
Breath tests in general—because they generally are non-invasive, fast, and cost-effective—have been the subject of several other Dark Daily e-briefings as well, including those about:
- Glucose monitoring;
- Hospital-acquired infections; and
- Monitoring of lung cancer therapy to name just a few.
Owlstone Medical’s ability to get backing from Britain’s NHS, as well as investments to the tune of $23.5 million (the most recent coming from Aviva Ventures) is a positive sign. That Owlstone Medical’s Breath Biopsy platform is credible enough to attract such respected collaborators in the cancer trials as the Cancer Research UK Cambridge Institute (CRUK), University of Cambridge, and Cambridge University Hospitals (CUH) NHS Foundation Trust is evidence that the company’s diagnostic technology is considered to have good potential for use in clinical care.
Medical laboratory managers and pathology group stakeholders will want to monitor these developments closely. Once proven in clinical trials such as those mentioned above, breath tests have the potential to supplant other medical laboratory diagnostics and perhaps lower the number of traditional biopsies sent to labs for diagnosis of cancer.
—Donna Marie Pocius
Related Information:
Five Tech Companies Advancing Against Cancer
Owlstone Medical’s ReCIVA Named Invention of the Year in Top 50 Digital Health Awards
One Day a Machine Will Smell Whether You’re Sick
Cancer Breath Biomarker: CRUK and Owlstone Start Multi-Cancer Trail
Researchers Determine That Individuals’ ‘Breathprint’ Are Unique; May Have Potential for Clinical Laboratory Testing When Coupled With Mass Spectrometry Technology
Pathologists may be interested to learn that everyone’s breath reveals a signature composition of metabolites that may reflect a lifetime of diet, state of health, illnesses, and exposure to chemicals
New research shows that a person’s “breathprint” is as unique as a fingerprint and may be as effective as bodily fluids in diagnosing diseases. That same research effort is showing that it is feasible to combine breath specimens and mass spectrometry to accurately identify disease. That could give clinical laboratories a new methodology to use when creating diagnostic assays.
These findings are part of a new study conducted by researchers at the Swiss Federal Institute of Technology (ETH Zurich) in Zurich. The study was published by the journal PLOS ONE. (more…)
World Economic Forum Publishes Updated List of 12 Breakthroughs in Fight against Cancer That Includes Innovative Clinical Laboratory Test (Part 1)
List also includes precision oncology, liquid biopsies, and early diagnosis of pancreatic cancer
Pathologists and clinical laboratory managers will be interested to learn that in a recently updated article the World Economic Forum (WEF) identified a dozen important recent breakthroughs in the ongoing fight to defeat cancer, including some related to pathology and clinical laboratory diagnostics.
The article noted that approximately 10 million people die each year from cancer. “Death rates from cancer were falling before the pandemic,” the authors wrote. “But COVID-19 caused a big backlog in diagnosis and treatment.”
The Swiss-based non-profit is best known for its annual meeting of corporate and government leaders in Davos, Switzerland. Healthcare is one of 10 WEF “centers” focusing on specific global issues.
Here are four advances identified by WEF that should be of particular interest to clinical laboratory leaders. The remaining advances will be covered in part two of this ebrief on Wednesday.
“Our study represents a major leap in cancer screening, combining the precision of protein-based biomarkers with the efficiency of sex-specific analysis,” said Novelna founder and CEO Ashkan Afshin, MD, ScD (above), in a company press release. “We’re not only looking at a more effective way of detecting cancer early but also at a cost-effective solution that can be implemented on a large scale.” The 12 breakthroughs listed in the World Economic Forum’s updated article will likely lead to new clinical laboratory screening tests for multiple types of cancer. (Photo copyright: Novelna.)
Novelna’s Early-Stage Cancer Test
Novelna, a biotech startup in Palo Alto, Calif., says it has developed a clinical laboratory blood test that can detect 18 early-stage cancers, including brain, breast, cervical, colorectal, lung, pancreatic, and uterine cancers, according to a press release.
In a small “proof of concept” study, scientists at the company reported that the test identified 93% of stage 1 cancers among men with 99% specificity and 90% sensitivity. Among women, the test identified 84% of stage 1 cancers with 85% sensitivity and 99% specificity.
The scientists published their study titled, “Novel Proteomics-based Plasma Test for Early Detection of Multiple Cancers in the General Population,” in the journal BMJ Oncology.
The researchers collected plasma samples from 440 individuals diagnosed with cancers and measured more than 3,000 proteins. They identified 10 proteins in men and 10 in women that correlated highly with early-stage cancers.
“By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate,” states a BMJ Oncology press release.
The company says the test can be manufactured for less than $100.
“While further validation in larger population cohorts is necessary, we anticipate that our test will pave the way for more efficient, accurate, and accessible cancer screening,” said Novelna founder and CEO Ashkan Afshin, MD, ScD, in the company press release.
Precision Oncology
According to the National Institutes of Health’s “Promise of Precision Medicine” web page, “Researchers are now identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that develop in totally different parts of the body can sometimes, on a molecular level, have a lot in common. From this new perspective emerges an exciting era in cancer research called precision oncology, in which doctors are choosing treatments based on the DNA signature of an individual patient’s tumor.”
This breakthrough is enabled by the emergence of next generation sequencing (NGS), wrote Genetron Health co-founder and CEO Sizhen Wang in a WEF blog post.
“These advanced sequencing technologies not only extend lifespans and improve cure rates for cancer patients through application to early screening; in the field of cancer diagnosis and monitoring they can also assist in the formulation of personalized clinical diagnostics and treatment plans, as well as allow doctors to accurately relocate the follow-up development of cancer patients after the primary treatment,” Wang wrote.
Based in China, Genetron Health describes itself as a “leading precision oncology platform company” with products and services related to cancer screening, diagnosis, and monitoring.
Liquid and Synthetic Biopsies
Liquid biopsies, in which blood or urine samples are analyzed for presence of biomarkers, provide an “easier and less invasive” alternative to conventional surgical biopsies for cancer diagnosis, the WEF article notes.
These tests allow clinicians to “pin down the disease subtype, identify the appropriate treatment and closely track patient response, adjusting course, if necessary, as each case requires—precision medicine in action,” wrote Merck Group CEO Belén Garijo, MD, in an earlier WEF commentary.
The WEF article also highlighted “synthetic biopsy” technology developed by Earli, Inc., a company based in Redwood City, Calif.
As explained in a Wired story, “Earli’s approach essentially forces the cancer to reveal itself. Bioengineered DNA is injected into the body. When it enters cancer cells, it forces them to produce a synthetic biomarker not normally found in humans.”
The biomarker can be detected in blood or breath tests, Wired noted. A radioactive tracer is used to determine the cancer’s location in the body.
The company hopes to begin clinical trials at the end of 2025, Genetic Engineering and Biotechnology News reported.
Early Diagnosis of Pancreatic Cancer
“Pancreatic cancer is one of the deadliest cancers,” the WEF article notes. “It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years.”
The WEF article authors highlighted an experimental blood test developed at the University of California San Diego School of Medicine.
The test is based on a technology known as high-conductance dielectrophoresis (DEP), according to a UC San Diego press release. “It detects extracellular vesicles (EVs), which contain tumor proteins that are released into circulation by cancer cells as part of a poorly understood intercellular communication network,” the press release states. “Artificial intelligence-enabled protein marker analysis is then used to predict the likelihood of malignancy.”
The UC San Diego researchers reported the results from their first clinical test of the technology in the journal Communications Medicine titled, “Early-Stage Multi-Cancer Detection Using an Extracellular Vesicle Protein-based Blood Test.”
The test detected 95.5% of stage 1 pancreatic cancers, 74.4% of stage 1 ovarian cancers, and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas, they wrote.
“These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests,” said co-senior author Scott M. Lippman, MD.
Look to Dark Daily’s ebrief on Wednesday for the remainder of breakthroughs the World Economic Forum identifies as top advancements in the fight to defeat cancer.
—Stephen Beale
Related Information:
Novel Proteomics-based Plasma Test for Early Detection of Multiple Cancers in the General Population
Precision Oncology: Who, How, What, When, and When Not?
Six Experts Reveal the Technologies Set to Revolutionize Cancer Care
Beyond Liquid Biopsies: How the Synthetic Biopsy Leads the Next Generation of Early Cancer Detection
A Proactive Way to Detect Cancer at Its Earliest Stages
Earli Detection: “Synthetic” Biomarkers Light Up Hidden Malignant Cancers
New Technique Detects 95% of Early-Stage Pancreatic Cancer
New Screening Tool IDs 95% of Stage 1 Pancreatic Cancer
Scientists Make DNA Discovery That Could Help Find Pancreatic Cancer Cure
Pancreatic Cancer Turns Off a Key Gene in Order to Grow
Early-Stage Multi-Cancer Detection Using an Extracellular Vesicle Protein-Based Blood Test
Promoter Methylation Leads to Hepatocyte Nuclear Factor 4A Loss and Pancreatic Cancer Aggressiveness
AXIM Biotechnologies Develops Diagnostic Test for Parkinson’s Disease That Uses Tear Drop Specimens and Returns Results in Less than 10 Minutes at the Point of Care
New non-invasive test could replace traditional painful spinal taps and clinical laboratory fluid analysis for diagnosis of Parkinson’s disease
Scientists at AXIM Biotechnologies of San Diego have added another specimen that can be collected non-invasively for rapid, point-of-care clinical laboratory testing. This time it is tears, and the diagnostic test is for Parkinson’s disease (PD).
The new assay measures abnormal alpha-synuclein (a-synuclein), a protein that is a biomarker for Parkinson’s, according to an AXIM news release which also said the test is the first rapid test for PD.
“The revolutionary nature of AXIM’s new test is that it is non-invasive, inexpensive, and it can be performed at a point of care. It does not require a lumbar puncture, freezing, or sending samples to a lab. AXIM’s assay uses a tiny tear drop versus a spinal tap to collect the fluid sample and the test can be run at a doctor’s office with quantitative results delivered from a reader in less than 10 minutes,” the news release notes.
A recent study conducted by the Michael J. Fox Foundation for Parkinson’s Research published in The Lancet Neurology titled, “Assessment of Heterogeneity among Participants in the Parkinson’s Progression Markers Initiative Cohort Using Α-Synuclein Seed Amplification: A Cross-Sectional Study,” found that “the presence of abnormal alpha-synuclein was detected in an astonishing 93% of people with Parkinson’s who participated in the study,” the news release noted.
“Furthermore, emerging evidence shows that a-synuclein assays have the potential to differentiate people with PD from healthy controls, enabling the potential for early identification of at-risk groups,” the news release continues. “These findings suggest a crucial role for a-synuclein in therapeutic development, both in identifying pathologically defined subgroups of people with Parkinson’s disease and establishing biomarker-defined at-risk cohorts.”
This is just the latest example of a disease biomarker that can be collected noninvasively. Other such biomarkers Dark Daily has covered include:
“With this new assay, AXIM has immediately become a stakeholder in the Parkinson’s disease community, and through this breakthrough, we are making possible new paradigms for better clinical care, including earlier screening and diagnosis, targeted treatments, and faster, cheaper drug development,” said John Huemoeller, CEO, AXIM (above), in a news release. Patients benefit from non-invasive clinical laboratory testing. (Photo copyright: AXIM Biotechnologies.)
Fast POC Test versus Schirmer Strip
AXIM said it moved forward with its novel a-synuclein test propelled by earlier tear-related research that found “a-synuclein in its aggregated form can be detected in tears,” Inside Precision Medicine reported.
But that research used what AXIM called the “outdated” Schirmer Strip method to collect tears. The technique involves freezing tear samples at -80 degrees Celsius (-112 Fahrenheit), then sending them to a clinical laboratory for centrifugation for 30 minutes; quantifying tear protein content with a bicinchoninic acid assay, and detecting a-synuclein using a plate reader, AXIM explained.
Alternatively, AXIM says its new test may be performed in doctors’ offices and offers “quantitative results delivered from a reader in less than 10 minutes.”
“Our proven expertise in developing tear-based diagnostic tests has led to the development of this test in record speed, and I’m extremely proud of our scientific team for their ability to expand our science to focus on such an important focus area as Parkinson’s,” said John Huemoeller, CEO, AXIM in the news release.
“This is just the beginning for AXIM in this arena,” he added. “But I am convinced when pharmaceutical companies, foundations, and neurologists see how our solution can better help diagnose Parkinson’s disease in such an expedited and affordable way, we will be at the forefront of PD research, enabling both researchers and clinicians a brand-new tool in the fight against PD.”
AXIM acquired Advanced Tear Diagnostics, Birmingham, Ala., in 2021. As part of this acquisition, it obtained two US Food and Drug Administration-cleared tests for dry eye syndrome, Fierce Biotech reported.
One of those tests was “a lateral flow diagnostic for point-of-care use that measures the level of lactoferrin proteins in tear fluid, which work to protect the surface of the eye. … Axim said that low lactoferrin levels have also been linked to Parkinson’s disease and that the assay can be used alongside its alpha-synuclein test,” Fierce Biotech noted.
Why Tears for PD Test?
Mark Lew, MD, Professor of Clinical Neurology, University of Southern California Keck School of Medicine, published earlier studies about using tear samples as biomarkers for Parkinson’s disease.
“It made sense to try and look at the proteinaceous [consisting of or containing protein] constituents of tear fluid,” Lew told Neurology Live. “Tear fluid is easy to collect. It’s noninvasive, inexpensive. It’s not like when you do a lumbar puncture, which is a much more involved ordeal. There’s risk of contamination with blood (saliva is dirty) issues with blood and collection. [Tear fluid analysis] is much safer and less expensive to do.”
In Biomarkers in Medicine, Lew et al noted why tears make good biomarkers for Parkinson’s disease, including “the interconnections between the ocular [eye] surface system and neurons affected in Parkinson’s disease.”
The researchers also highlighted “recent data on the identification of tear biomarkers including oligomeric α-synuclein, associated with neuronal degeneration in PD, in tears of PD patients” and discussed “possible sources for its release into tears.”
Future Clinical Laboratory Testing for Parkinson’s
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s. It affects nearly one million people in the US. About 1.2 million people may have it by 2030, according to the Parkinson’s Foundation.
Thus, an accurate, inexpensive, non-invasive diagnostic test that can be performed at the point of care, and which returns clinical laboratory test results in less than 10 minutes, will be a boon to physicians who treat PD patients worldwide.
Clinical laboratory managers and pathologists may want to follow AXIM’s future research to see when the diagnostic test may become available for clinical use.
—Donna Marie Pocius
Related Information:
Parkinson’s Disease Biomarker Found
Tear Drop Test is First Rapid, Point-of-Care Diagnostic for Parkinson’s Disease
New Test Aims to Spot Signs of Parkinson’s Disease within a Tear Drop
Motivations for Using Tears to Confirm Parkinson’s Disease Diagnosis
