Onco Track

Colorectal cancers are a very heterogeneous group of cancers and not all of them respond to the same drugs in the same way. By collecting tumour samples from patients and then analysing them in the laboratory, the OncoTrack project found molecular fingerprints of those tumours and then correlated them to how these tumours respond to various drugs. ###The project’s outputs are already helping doctors in choosing the right treatment for the right patient, and could also help in the future search for more effective drugs. As a result of the project, two spin out companies have been created and several patents filed, demonstrating tangible socio-economic benefits. In an interview with the IMI Programme Office, project coordinator, David Henderson of Bayer, and academic coordinator Hans Lehrach of the Max Planck Institute for Molecular Genomics, explain why all this wouldn’t have been possible without the public-private collaboration brought by IMI. ‘This was an extremely complex project,’ said Henderson. ‘In order to be successful with this degree of complexity you need a lot of know-how and a lot of detailed knowledge, and you can never find all of this in one place. So the big advantage of a public-private partnership is that you can bring in the different types of detailed knowledge that are available in an industrial setting, in a biotech start-up or in an academic setting. When you bring these together, the sum becomes much greater than its individual parts.’ Read the full interview

Scientists from IMI’s ONCOTRACK project have identified a new way of tackling colon cancer; their findings are published in the journal Cell Reports. Colon cancer is the third most common cancer and the fourth most common cause of cancer deaths worldwide. ###Research has shown that cancer stem cells, which multiply and differentiate into different cell types like normal stem cells, play a key role in driving the growth of colon cancer tumours. They are also thought to be behind relapses, when cancer returns following treatment. In this study, researchers studied the sequences of genes in cancer stem cells, and found a that cancer stem cell survival is controlled by a specific feature of the ‘Hedgehog’ signalling pathway which allows cells to respond to external signals and inhibits stem cell differentiation. Targeting the Hedgehog pathway in a similar way has delivered promising results in early-stage research on pancreatic and breast cancer cells. ‘The targeted inhibition of the Hedgehog signalling pathway, used in combination with other standard treatments to shrink tumours, may provide a new strategy for the elimination of cancer stem cells and the prevention of cancer recurrence,’ said the first author of the paper, Joseph Regan of the Charité Comprehensive Cancer Center. ‘Future research will set out to better define the downstream signalling components of the pathway and further investigate how Hedgehog signalling controls cancer stem cell survival.’

Colorectal cancer is the third most frequently occurring cancer worldwide and, at an advanced stage, one of the most common causes of death. It takes numerous forms, with not all such cancers responding to the same drugs in the same way.### To improve responses of colorectal tumours to treatment and increase survival rates, IMI’s OncoTrack project collected tumour samples from 106 patients. These were grown and analysed to identify biomarkers and create molecular fingerprints for each one. Researchers then tested the response of the tumours to different drugs and correlated the molecular fingerprints and responses. This made it possible to predict whether a drug will be effective on a specific tumour. In this way, the OncoTrack researchers discovered sets of biomarkers that can predict the effectiveness of two common means of colorectal cancer treatment: Cetuximab, which stops proteins on the surface of cancer cells from causing the cells to divide and grow, and the chemotherapy drug 5FU. ###

‘The biological models of colon cancer that the consortium developed are especially well characterised and are already being used by some pharma companies for drug discovery and development projects,’ says David Henderson, who coordinates the project on behalf of Bayer AG in Germany. Growth of the tumours took place in 3D tissue culture systems and through xenografts – tissue grafted onto mice, which creates a strain of the disease adapted to mice. Use of the models developed under OncoTrack has the potential to bring about long-term benefits. One biotech company has been developing and refining a computer-based drug response prediction approach which may ultimately provide a commercial diagnostic service. ‘The xenograft models are available on a commercial basis and a new company was spun out from the project to capitalise on the technologies surrounding use of the 3D culture models in drug development,’ says Henderson.

• Read the full story

Colorectal carcinomas are a very heterogeneous group of cancers and not all of them respond equally to different drugs. Up until now, doctors have decided on which drug to use based on the tumour gene mutations. However, the mutation status alone is not specific enough.### To be able to predict a tumour’s response to certain drugs more accurately, IMI’s OncoTrack project set out to produce molecular fingerprints of different tumours and correlate the different fingerprints to how the tumours respond to various drugs. In the process, they identified two new biomarkers for colorectal cancer which could lead to more personalised and effective treatments for patients with this disease.

The study, which was recently published in the journal Nature Communications, was one of the largest public-private collaborations in this field to date. By bringing together academic institutions, SMEs and the pharmaceutical industry, OncoTrack scientists first collected tumour samples from over 100 colorectal cancer patients at different stages of the disease. They grew these tumours in tissue culture systems, as well as in special mouse strains, and proceeded to analyse them in the lab. In particular, the scientists looked for biomarkers, i.e. molecules that are typical of the different tumour sub-groups. Based on this analysis, they were able to produce molecular fingerprints for all of the tumours. Next, they tested how the tumours respond to different drugs and correlated various tumour fingerprints with their response to the different clinical compounds. Among other things, they discovered two biomarkers that can predict the effectiveness of two drugs commonly used to treat this disease: Cetuximab, which inhibits the receptor for the epidermal growth factor, and the chemotherapy drug 5FU. ‘The extensive molecular and drug sensitivity datasets generated within this study are a highly valuable resource,’ said Bodo Lange, CEO at Alacris Theranostics, one of the OncoTrack project partners. ‘Our findings provide major new insights into the molecular landscape of colorectal cancer and have the potential to guide treatment decisions.’

• Read the OncoTrack press release
• Read the project factsheet

An international team of scientists has developed a smartphone-based microscope that can analyse DNA sequences and spot genetic mutations in samples of bowel cancer cells and tissues. This information is vital to help doctors determine which treatments are likely to work in a patient, and the new device will make this technology more readily accessible to people in remote areas and poorer parts of the world. ###The novel device, funded in part through IMI’s bowel cancer project OncoTrack, is described in the journal Nature Communications. DNA sequencing is increasingly used in cancer treatment; if you know which mutation is driving a patient’s cancer, you can determine which treatment is most likely to beat it. However, to get this information, doctors usually have to send cell and tissue samples away to large, specialist laboratories. This new microscope, which is created by 3D printing, would allow doctors to carry out the test on the spot. When hooked up to a smartphone, it can read the DNA sequence of a tumour and flag up specific mutations. The researchers estimate that if produced in large quantities, the cost of manufacture of the microscope could be as low as USD 500 (EUR 466). For comparison, prices for standard microscopes used for sequencing start at USD 10 000 (EUR 9 300). Although the researchers focused initially on cancer, they believe the microscope could play a vital role in diagnosing infectious diseases. ‘Antibiotics are effective against bacteria. But now we are losing that weapon when bacteria become resistant,’ said Mats Nilsson of the Universities of Stockholm and Uppsala. ‘However, if we could look at the DNA level and find out if a bacterium is sensitive to a certain type of antibiotics, we could choose the right treatment from the very beginning. This is where I think this concept has its great strength.’

• Read the press releases of Stockholm University and the University of California

IMI cancer project OncoTrack and life sciences data infrastructure ELIXIR are exploring how they could collaborate to ensure the provision of data storage and discovery services for data generated by the project.### OncoTrack brings together pharmaceutical companies, academics and small and medium-sized enterprises (SMEs) in a quest to develop new approaches to identifying markers for colon cancer, something which will help to improve diagnosis and treatment of the disease and may ultimately contribute to increased chances of survival. As part of this effort, the project is generating large amounts of data. ELIXIR could help OncoTrack to store and manage this data safely and securely through its European Genome-Phenome Archive (EGA). OncoTrack and ELIXIR are also exploring options for the long term management of data in TranSMART, which OncoTRACK is already using for data analysis through IMI’s eTRIKS project. Niklas Blomberg, ELIXIR Director said: ‘We are delighted to collaborate with OncoTrack, a shining example of the potential that big data has for advancing medical knowledge. This collaboration could provide a model for how translational data can be made available for long term re-use by the biomedical research community.’

Researchers working on IMI’s cancer project OncoTrack have teamed up to launch a spin-off company called Cellular Phenomics & Oncology  Berlin-Buch GmbH (CPO).### Founded by Christian Regenbrecht and Reinhold Schäfer of Charité Universitätsmedizin Berlin and Jens Hoffmann of German biotech company Experimental Pharmacology & Oncology, CPO will establish a library of patient-derived, three-dimensional cancer cell cultures that can be used in drug research and development. CPO will also work with other partners to develop the technology to identify personalised treatments for cancer patients. In the beginning, the company will focus on developing models of melanoma (skin cancer), breast cancer, lung cancer, head and neck cancers, and colorectal cancer. Christian Regenbrecht and Reinhold Schäfer are the academic leaders of OncoTrack’s cell culture work package, and the experience of creating cell cultures of human colorectal cancers under the project will be valuable when setting up the company’s workflows. All three scientists will remain with their original organisations and so will continue to work on OncoTrack. Meanwhile, CPO may well join the project in its own right.