Biomarkers: Embracing a Holistic View Is Key to the Future of Precision Medicine

We are entering an era where healthcare as we know it is going to be revolutionized.  We’re beginning to realize the potential that biomarkers hold for the world of medicine. By enabling medical scientists to stratify patients into clear, targeted groups categorized by their susceptibility to various diseases and likely responses to treatment, these biomarkers hold the key to ending one-size-fits-all treatment of disease.

Most coverage of novel biomarkers to date has been focused on genetics, or so-called Molecular Diagnostics; how a patient’s genetic signatures can indicate their susceptibility to a disease, its possible severity, and what treatments may prove most effective. With genome sequencing reaching new levels of maturity, now is the time to recognize that genomic indicators alone will only drive the advent of precision medicine so far. 

Other ‘omic’ areas, such as proteomics, lipidomics and metabolomics, coupled with environmental and lifestyle factors, will contribute even more to differences in disease risk and drug response. Whether a person smokes, for example, has been proven to have a significant demonstrable impact on their response to certain treatments.

Understanding and embracing the potential of these non-genetic biomarkers can hold the key to a new era of efficient, predictive and precise medical science and have a significant impact on clinical decision making – ensuring the ‘right drug’ is administered to the ‘right patient’ at the ‘right time’.  Precision medicine requires precision diagnostics.

The missing piece

At SCIEX, our purpose is to deliver new technology that enables translational researchers to break new ground in biomarker discovery and accelerate the path to precision diagnostics in pathology labs around the world. These mass spectrometry-based technologies are used to target a wide array of diseases, including pediatric and gynecological cancers, cardiac diseases, lupus, dementia and rheumatoid arthritis.    

Two areas in particular have been the focus of our effort: proteomics; and metabolomics. Proteomics is vital as proteins can provide a comprehensive link between the genome, external factors and the phenotype – crucial in the study of many cancers and longer-onset diseases in which a multitude of factors influence susceptibility and best possible treatments. Metabolomics, meanwhile, gives us the most representative picture of what is going on in an organism in the here-and-now; the behavior of which often acts as a signifier of early stage onset of diseases that would have no genetic markers and produce no early changes in the proteome. 

The use of genetic and non-genetic markers of disease risk, diagnosis, response to therapy and prognosis to improve patient stratification and drug targeting has the potential to be truly transformative for patients. By giving the right drug to the right patient at the right time, not only do chances of improved patient outcomes increase; drug failure rates will reduce, which provides added value to health systems and payors. At the same time, patient experience will ultimately be improved. The historic trial and error approach to treating complex diseases such as systemic lupus erythematosus (SLE) could become a thing of the past, as we understand what works in different cohorts of patients, with interrelated omic and lifestyle factors.  

Scaling up

To realize this potential, biomarkers will need to be discovered, verified and validated at an industrial scale – something that is very challenging to do without significant investment and a commitment to collaboration from across various parts of the industry.  

The Stoller Biomarker Discovery Centre at the University of Manchester opened in 2016 and has subsequently become Europe’s leading facility for the discovery of biomarkers. Funded through a partnership between the Stoller Charitable Trust, the UK Medical Research Council and SCIEX, it was designed for systematic clinical research on a scale rarely seen before and focuses on diseases ranging from Alzheimer’s to psoriasis to coronary heart disease.

The key to the Stoller Centre’s success is scale. It is working 24 hours a day, seven days a week and is using innovative techniques and technologies to continuously improve the rate at which it can process samples.  Using SWATH acquisition on a mass spectrometer – a technique that allows comprehensive detection and quantification of virtually every detectable protein in a sample – Stoller is now able to run thousands of samples in parallel, significantly increasing the speed and confidence with which biomarkers can be detected.

One of the Centre’s key areas of focus is currently ovarian cancer – a disease which has extremely low survival rates when detection happens in stage 3 or 4, making predictive detection vital. Having built up a bank of 1,200 serial serum samples from ovarian cancer patients, the team at Stoller was able to test every sample in just 12 weeks, running 3,600 SWATH injections with only half of their capacity dedicated. This has yielded new biomarkers at a rate that would previously have been impossible using traditional mass spectrometry, and which will have a potentially transformative impact on the early detection of ovarian cancer for patients worldwide.

The future

When it comes to the potential impact of genetic and non-genetic biomarkers, advances in biomarker discovery are just the beginning. It won’t be long before labs will offer direct-to-consumer testing for multi-analyte biomarker panels from a single drop of blood, acquired in the home and sent through the post.  As a precedent, just look at the recent revolution in DNA testing to trace genetic heritage.  However, unlike genetic testing, non-genetic biomarkers should be measured monthly so that deviations from the steady-state baseline can be flagged.  From there, it’s not too much of a stretch to run a massively-multiplexed omics profile and obtain a direct, tailored assessment on their current wellness and susceptibility to various diseases, which they can use to make informed choices about their health, lifestyle and need for clinical intervention. Underpinning all these advances, data analytics and machine learning will be key to making biomarkers become an integral part of daily life and the foundation of public health tools worldwide.

For this vision to become reality it will also require an evolution of the current governmental regulatory pathways and testing reimbursement mechanisms in countries around the world.  Achieving the right balance between the safety, efficacy and security of diagnostic testing, and accelerating the use of new biomarkers, is not trivial.  Nor is the shift for payors from the cost of illness to the cost of wellness. 

The expectations for healthcare are changing. We need to adopt a more holistic approach to the use of biomarkers if we are to deliver precision medicine that is truly targeted and predictive. The future lies in advancing high-throughput technologies in the lab and combining this with artificial intelligence and machine learning to overlay regularly measured biomarker profiles with patient metadata. In doing so, this could drive the evolution of biology and medicine exponentially and help realize the promise of precision medicine, with biomarkers using omics data in combination with environmental and lifestyle factors to drive routine clinical practice – ultimately leading to huge benefits for patients and the healthcare industry around the world.

About the author

Aaron Hudson is Vice President of Global Marketing and Clinical Diagnostics at SCIEX, a Danaher operating company and a global leader in the accurate quantification of molecules.