NMR-based metabolomics: Making "precision medicine" a reality

What insights can NMR-based metabolomics provide into how cancer operates, and how therapeutic approaches might be tailored to the individual? We talk to Prof. Tone Frost Bathen about why she has valued NMR throughout her research career.So how does the knowledge obtained with NMR-based metabolomics help in studying cancer? Prof. Bathen says that it’s the detailed picture provided by the technique that helps researchers understand the disease’s complex biochemistry.

“My research is mostly focused on breast and prostate cancer, which are the two most common cancers globally,” she explains. “Although treatment options and survival rates have increased a lot in recent decades, there are still a number of challenges, one of which is the heterogeneity of cancer – it simply varies a lot between people, and even within a single tumor.”

This heterogeneity, she believes, is one of the problems that NMR-acquired information on biomarkers can help to solve. “The first way it can help is simple, at least in principle – we can use biomarkers from biological samples such as serum and urine to flag people who are at risk of developing a disease, or who are already in the early stages.”

The second benefit relates to the expanding interest in precision medicine, “The idea is that, with the help of NMR as well as other molecular methods, we can use these biomarkers to classify patients into groups that will benefit from particular therapeutic approaches – what in the field we call stratification,” she says. “So, for example, we could predict a patient’s likely response to an intervention and ensure that not only do they get the best treatment, but that they are not over-treated.” This logic also works the other way too, she mentions: “So we could understand how different treatments might affect their metabolic profile, and thus the likelihood of later complications such as cardiovascular disease.”

Professor Tone Frost Bathen has been in research for 30 years, and during that time has relied on the power of magnetic resonance techniques such as nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) to study disease-related metabolites. This practical expertise has led to her role as head of a facility that serves researchers at NTNU, St Olav’s University Hospital in Trondheim, as well as further afield in Norway and Denmark.

Better results from stronger collaboration

Prof. Bathen is enthusiastic about these research connections: “The network we have here is very important,” she points out. “We not only help researchers run their samples, but we guide them on spectral interpretation, and help them address their research questions using bioinformatics approaches.”

Such a collaborative approach has been particularly important over the last two years, because of the impact of Covid-19. She says: “Covid-19 is not constrained by borders, and neither is our work using NMR. For example, our collaborations during the pandemic have helped us develop standardized methods and optimized NMR sequences, which in turn lead to more meaningful results based on larger cohorts of patients and biobanked samples.”

Unparalleled detail and productivity

The majority of Prof. Bathen’s research has been focused on cancer and, right from the start, she appreciated the value of NMR: “When we began our cancer-related research in mid-90s, we were one of the first groups to analyze intact cancer tissue using the magic-angle spinning (MAS) technique – and we’re still using it today.” Of course, the equipment has improved in many ways since then, and today her facility offers a 600 MHz Avance IVDr spectrometer from Bruker for in vitro studies, as well as a Bruker Biospec 70/20 USR Avance III system for in vivo imaging – both of which offer unparalleled detail on the metabolites found in cancerous cells.

One of the main reasons that Prof. Bathen is an advocate of the Avance IVDr platform is that it is tailored for preclinical screening and has a high level of automation. “To put it simply, we can analyze a lot of samples in a short timeframe,” she says. “This equipment also gives us a lot of detail on the lipoprotein subfractions of our samples – far more than you’d get from traditional clinical chemistry tests.”

The quantitative, reproducible nature of NMR data is also important for her, and she points out that, “When applied to cancer research, having this data provides us with a detailed signature for cancer-related metabolites, whether we’re looking at solid tissue samples or biofluids.”

Using biomarkers to develop precision medicine

So how does the knowledge obtained with NMR-based metabolomics help in studying cancer? Prof. Bathen says that it’s the detailed picture provided by the technique that helps researchers understand the disease’s complex biochemistry.

“My research is mostly focused on breast and prostate cancer, which are the two most common cancers globally,” she explains. “Although treatment options and survival rates have increased a lot in recent decades, there are still a number of challenges, one of which is the heterogeneity of cancer – it simply varies a lot between people, and even within a single tumor.”

This heterogeneity, she believes, is one of the problems that NMR-acquired information on biomarkers can help to solve. “The first way it can help is simple, at least in principle – we can use biomarkers from biological samples such as serum and urine to flag people who are at risk of developing a disease, or who are already in the early stages.”

The second benefit relates to the expanding interest in precision medicine, “The idea is that, with the help of NMR as well as other molecular methods, we can use these biomarkers to classify patients into groups that will benefit from particular therapeutic approaches – what in the field we call stratification,” she says. “So, for example, we could predict a patient’s likely response to an intervention and ensure that not only do they get the best treatment, but that they are not over-treated.” This logic also works the other way too, she mentions: “So we could understand how different treatments might affect their metabolic profile, and thus the likelihood of later complications such as cardiovascular disease.”

Taking NMR from the lab to the clinic

In conclusion, Prof. Bathen thinks that NMR offers distinct advantages in the challenge of ‘translating’ metabolomics approaches from being interesting research tools to delivering genuine value in healthcare. “Because highly detailed data can be acquired quickly and non-invasively, whether by using biofluid samples or through in vivo imaging, we could very easily take methods used in the lab and apply them to decision-making in a clinical scenario,” she says. “And that offers great opportunities for helping people to live longer, healthier lives.”

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Since 2006, Prof. Tone Frost Bathen has worked at the Norwegian University of Science and Technology (NTNU) in Trondheim, Norway, where she currently leads the Magnetic Resonance Cancer Group. The group’s main interests are focused on personalized medicine and studies of functional and metabolic properties of cancer, using magnetic resonance imaging, positron emission tomography, and magnetic resonance spectroscopy, more commonly referred to as NMR. Currently, Prof. Bathen’s research activities focus on breast and prostate cancer and establishing better diagnostic tools for stratification of patients to treatment and treatment monitoring.

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