The NMR machine in the lab of James Larkins, with samples lined up to be analysed

Following the cancer metabolomic breadcrumb trail

To detect cancer earlier, researchers are working on a variety of minimally invasive methods that are able to pick up the earliest signs of cancer. These include measuring molecules released from cancers into the blood, such as DNA, proteins or metabolites, or by imaging. However, each method has its own advantages and disadvantages. For example, several cancer early detection methods focus on genetic material, such as new technologies that identify cancer-specific circulating tumour DNA (ctDNA) in the blood. However when using ctDNA alone in cancer detection, it may be challenging to detect the smallest, early tumours that release less DNA. Similarly for imaging, the very earliest cancers may be missed because they are simply too small to be seen using current imaging technologies.

Department of Oncology researcher, Dr James Larkin, is working with his collaborators to take a combination approach to the early detection of cancer, by looking at changes of metabolic molecules and how this might contribute to detecting cancer, which can be used alongside the existing approaches.

Metabolomics deals with the measurement of metabolites – the small molecules that are involved in the process of cellular metabolism. Our bodies have a balance of metabolites that we maintain through normal cellular processes like building proteins and producing energy. Cancer cells disrupt the metabolic balance that is normally present and Dr Larkin is investigating whether we can test for these metabolite changes using blood tests. If so, this may open a route to identify the presence of cancers at their earlier stages when they are more treatable.

About the study

Dr Larkin is working alongside the SCAN Pathway, to access blood samples from patients who are displaying vague symptoms that are non-specific, but may be a result of cancer. He hopes that he may complement the success of this project, by analysing the metabolic fingerprint of each patient, to see if there are any differences in their metabolome that would suggest cancer.

Thus far, Dr Larkin’s metabolomic approach has been applied successfully in Multiple Sclerosis patients. In a previous study, he found that metabolomic evidence identified which patients were progressing to the later stages of MS, before even the doctors or patients could identify it themselves.

Now, Dr Larkin is looking at applying this approach to cancer via the SCAN pathway. Specifically, he is using nuclear magnetic resonance (NMR) to identify the full metabolic fingerprint of a patient.

Dr James Larkin, Senior Postdoctoral Researcher on the project, said:

“NMR is like a tuning fork for molecules. Imagine hitting thousands of different tuning forks, all at once. If you analysed the sound carefully, you could work out which tuning forks you hit. NMR uses magnets and radio waves instead of sound, and all the different tuning forks are all the different metabolites, but the principle is very similar. This approach allows us to not only see which metabolites are present, but in what quantity as well, which in turn allows us to compare the profile to that of a healthy patient.”

An example of what you might hear in one of these NMR experiments can be heard through the Soundcloud below

The benefit of using NMR is that, rather than looking at one or two targets that might suggest the presence of cancer, something that can limit many biomarker approaches, it looks at the whole metabolic profile of a patient at once.

“The ultimate goal of this work is to produce a test for cancer that GPs can prescribe in the surgery. If a patient presents with suspicious symptoms, an inexpensive blood test using metabolomics could give a probability of cancer presence, allowing us to prioritise patients for further tests” says Dr Larkin.

Dr Larkin’s upcoming paper which will be published later this year is looking at the viability of using metabolomics on the SCAN patient cohort to identify who has cancer. From their data, he is developing classification models that show the difference between the metabolic profiles of patients with and without cancer, so that they can be applied to other patients more widely.

He hopes that after this, he will be able to use the metabolomics approach to create specific tests for individual types of cancer. This is theoretically possible, as the metabolic profile of an individual cancer cell is unique, which means that Dr Larkin and his team can match the metabolic fingerprint to a specific type of cancer, such as those in the lung or pancreas. This would be a huge benefit to doctors, as full body scans are expensive, can expose the patient to unnecessary radiation, and the cancer is not always easily identified on a scan.

Outcomes of this work will be published later this year.

This work has been funded by the Oxford Centre for Early Cancer Detection, Cancer Research UK and the Medical Research Council.