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, and not all cancers respond to the same kind of treatment. This is because tumours undergo genetic changes as they grow and spread, and these changes can vary even between patients with the same type of cancer. 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.
By bringing together academic institutions, SMEs and pharmaceutical companies, 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.
New 3D models of colon cancer, and other achievements
Growth of 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. Analysis covered the genetic material, RNA molecules and in some cases, the proteins of the tumours. These biological models are now considered as some of the best characterised in the field, and are already being used by pharmaceutical companies in their drug discovery and development projects.
Other important outputs generated by the project include:
- a biorepository of patient-derived 3D cultures and patient-derived xenograft models;
- a database which contains part of the data generated by the project, with plans to complete it in the near future.
Two spin outs and various patents
The project also resulted in two spin-out companies. One of them was created in 2014 to commercialise the technology of 3D tissue culture systems or organoids. Generated from the tumour tissue, organoids are groups of cells that grow in the culture dish, remain small, and mimic a lot of the biology of the tumour. They are potentially quite useful to pharma companies and this spin-out has been set up to commercialise this as a basis for drug testing.
The second company was set up in 2018. It spun out from a group at the University of Paris, and intends to commercialise OncoTrack’s technologies developed to improve diagnostic procedures.
One of the major goals of OncoTrack was also to find better ways to diagnose cancer, and some of the partners have refined the technologies that they have been using. Several patents have been filed as a result.
Benefits to patients
OncoTrack project outputs are already benefitting patients. For example, the analysis of tumour samples of more than 100 patients, which was done as part of this project, is now available to the doctors treating those patients. Furthermore, for drugs which are already used in the clinic, such mutation analysis is now becoming routine, helping doctors choose the right drug for the right patient.
Additionally, one of the academic partners, the Medical University in Graz, is using the 3D culture models, which were developed during the project, in an experimental setting in the clinic in order to find drugs that can potentially help patients for whom no treatment is available.
For the benefit of industry, academia and SMEs
The academic institutions in the project benefitted from access to the pharmaceutical companies’ resources, such as drugs which were tested during the project. They also got a lot more information about mechanisms of drug action then they otherwise would have. In turn, the pharmaceutical industry is benefitting from the information, materials and biological models developed during the project.
Both academia and industry partners gained a lot from collaborating and exchanging different viewpoints and perspectives. For example, academics have learned more about how the industry works, and the industry has benefited from academic expertise. The connections which have been established will last well into the future.
Finally, the SMEs in the project benefitted from increased visibility and reputation, as well as new contacts with both industry and academic partners. Participating in OncoTrack accelerated their business expansion and helped them enter into new markets.
The information and models created during OncoTrack are now available for future research projects. In fact, several OncoTrack partners are continuing to work together in new pan-European projects, such as the Future Health initiative. Additional new projects, funded by national or local agencies, have been initiated by some of the academic partners.
Read the interview with project coordinators