Laboratory tests are insufficiently predictive of cancer drugs’ activity in humans. The rate of failure to take novel drugs from the laboratory to humans, and then to registration for clinical use, has been very high. According to some estimates, between 90 and 95 per cent of drugs that went into clinical trials had no to only marginal effect on patients’ tumours. One of the reasons for that is that cancer is a very complex disease, both genetically and in terms of the tumour's interaction with the body. The models which scientists have been using in the laboratory to predict the success of a cancer drug in patients do not capture that complexity. IMI’s PREDECT project set out to change that.
By bringing together top researchers from nine pharmaceutical companies, eight academic institutions and three SMEs, the project developed and characterised new laboratory models which should better capture the complexity of the disease and so predict drug efficacy more reliably. This could eventually lead to a lower failure rate in the development of new cancer drugs for the benefit of patients.
Models that capture tumour architecture
The most common way of investigating tumours in the laboratory is by growing cancer cells on plastic dishes. However, this method captures neither the three-dimensional architecture of tumours, nor their heterogeneity, nor the interactions between cells and their surroundings.
In order to better capture the three-dimensional nature of cancers, PREDECT project scientists further developed and reciprocally compared an array of spheroid models of tumour cells, as well as models generated from freshly collected tumour tissue. As an extension of this effort, the project initiated a biennial conference called ‘Goodbye Flat Biology’, under the auspices of the European Association of Cancer Research (EACR), to promote a continued dissemination of the concept that architectural aspects of cancer are very important in building good models.
Reducing use of animals in research
Other important tumour aspects are that they are genetically diverse and that they are in constant interaction with their host. In order to capture that heterogeneity within the native microenvironment of the tumour, PREDECT project scientists developed a method to obtain very thin slices of tumours. These slices capture the complexity that is so essential for validating that a particular drug is going to work in the future.
The tumour slicing method developed by the project significantly reduces the use of animals and required research time. Whereas in the past 18 animals had to be used to obtain 18 tumour samples, now 18 to 20 slices can be obtained from a single tumour. For this work, PREDECT scientists won one of AstraZeneca’s awards for the use of tumour slices as an innovative in vitro platform to reduce animal use.
‘Game-changer’ in breast cancer research
The project also developed a much-improved animal model to study oestrogen-receptor positive breast cancer, one of the most commonly diagnosed breast cancers. Experts wrote that this model was a ‘game-changer’, with the potential to lead to new treatments. The academic partners who developed this model now organise a course on this technique to enable other researchers to use it.
Transfer of technology and other accomplishments
In addition to the successes mentioned above, other top project outputs include:
- a collection of open access papers, four of which include detailed protocols on the making of new laboratory models developed within the project;
- a collection of more than 30 000 images generated from a series of 16 oncology marker stainings done on all models created within the project - there are plans to make these available to the research community in the future;
- transfer of important technology, from SMEs and academia to pharma companies, which could increase the industry’s success in the development of future drugs.
For the benefit of industry, academia, SMEs
The academic community is benefiting from gaining a deeper understanding of challenges in the development of complex cancer models, and from the new models which were created within the project. Thanks to this project, they also gained a better understanding of the thinking, constraints and needs of the industry.
Industry, academia and SMEs are benefitting from the transfer of technology which occurred within the project. For example, a Portuguese SME transferred their bioreactor technology to pharma companies. Thanks to this, pharma companies changed the way they work, and the SME expanded its business and gained important new customers.
The pharmaceutical industry is also benefitting from other technologies and models developed within the project, including tumour slices, as well as a range of 3D and animal models.
All project participants are also benefitting from the collaborative network which was established as part of the project.
Although this project achieved significant breakthroughs, there are still many questions left unanswered. The knowledge and insights gained during the project have solidified new collaborations, and may also lead to new projects in the future.