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Mass spectrometry imaging

Building a 'Google Earth' of cancer

The Grand Challenge, a new Cancer Research UK initiative, aims to overcome the biggest challenges facing cancer researchers in a global effort to beat cancer sooner

Funded through Cancer Research UK's Grand Challenge scheme, NPL's Professor Josephine Bunch leads a group of international and multidisciplinary chemists, physicists and biologists from the UK to develop a reproducible, standardised way to fully map tumours with extraordinary precision.

Now at the end of its first year, this ground-breaking project has progressed with impressive speed and achieved some remarkable results. These advancements are set to transform our understanding of cancer and open the door to new and better ways to diagnose and treat the disease.

The world's first 'Rosetta Stone' of cancer cell metabolism

In the same way cartographers build maps of cities and countries to help people get around, scientists build maps of tumours to better understand their inner workings. But despite significant advances in technology and our understanding of cancer, our tumour maps remain incomplete. What's missing is our ability to see down to the very core of cancer cells and understand how changes in their metabolism can impact their overall state and function within a tumour. No one has ever mapped tumours in this level of detail before – until now.

The 'Rosetta' team are focusing on breast, bowel and pancreatic tumours, as well as investigating an aggressive type of brain tumour. They are working to capture changes to these metabolites as tumours develop or respond to treatments while simultaneously recording information about the cell's exact location within the tumour.

Superimposing these data with maps revealing information about the underlying genetics of these cells will produce the world's first 'Rosetta Stone' of cancer cell metabolism – a high-resolution metabolic map that offers unprecedented insight into a cell's biochemical state. This cutting-edge approach is generating vast amounts of data, which will be made freely available to the research community, providing a Google Earth-type view of a tumour, on a scale that we have never known before.

The Rosetta project

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The impact

The scale and precision of the Rosetta team's approach to mapping tumours is truly remarkable – combining exceptionally specialist instruments and methods and applying them to the cancer field for the very first time. By creating such detailed representations of tumours, they are set to transform our understanding of cancer.

First year of success – identifying drug resistance

The Rosetta team developed an imaging pipeline that produces an ultra-high resolution picture of the metabolism of tumours – allowing the team to map the distribution of cancer drugs within a tumour, as well as changes in cell metabolism.

In year one, by analysing pre-clinical tumours treated with different AstraZeneca cancer drugs, the Rosetta team were able to provide valuable insight into the distribution of the drugs within the tumour. Importantly the results highlighted hotspots of drug resistance, illustrating the power of the imaging techniques, which can revolutionise understanding of drug penetration and treatment resistance.

Building on this extraordinary preliminary result, the team is now focused on precisely optimising every step in their pipeline to improve the resolution and reproducibility of their unique tumour maps.

Read our article Mapping tumours – a new direction for cancer treatment which appeared in PharmaTimes online in May 2019.

 

 

We are very excited about the results that we are obtaining as a part of Rosetta consortium. Combining mass spectrometry imaging with our conventional approaches is allowing us to finally dissect the factors determining the breast cancer metabolic heterogeneity and specifically what role MYC plays in it. We are very much looking forward to seeing how the data from our pre-clinical models will translate into human breast cancer samples.

Dr Mariia Yuneva - Francis Crick Institute

Meet the team

Grand Challenge team

I'm very excited about the progress we have made. We now have data to suggest that the major mutation that occur in colorectal and pancreatic cancer drives metabolic signature that can be easily identified using image based mass spec approaches. This shows the power of this methodology to stratify cancers. Going forward I'm looking forward to seeing if we can see if we can use these approaches to predict therapeutic responses in these cancers.

Professor Owen Sansom - Beatson Institute