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How Oncode-PACT is bringing new cancer medicines closer with 325 million in Growth Fund money

How can you ensure that more experimental drugs reach the finish line? At the moment, only one in twenty cancer drugs that are tested on humans makes it to the market. This is an enormous loss for patients and society. With a grant from the National Growth Fund, Oncode-PACT aims to efficiently select the best compounds, so that more experimental medicines reach the finishing line. Among others, Leiden chemists, pharmacologists, biologists and computer scientists are working together to achieve this. Mario van der Stelt, Professor of Molecular Physiology and principal investigator at the Oncode Institute, explains how.

He received the liberating text message during a meeting on 14 April, early in the afternoon. The Oncode-PACT consortium, with Van der Stelt as one of the architects, will receive 325 million euros from the National Growth Fund over the next eight years. With this money, around fifty companies and institutes can work on their plan to develop cancer medicines faster and better. Among them are many scientist from the Science Faculty of Leiden University. 'I was not allowed to say anything after that text message because it was a secret until the Minister's press conference had finished,' says Van der Stelt.

Earlier determination of whether an experimental drug can become a medicine

What problem will Oncode-PACT solve? Van der Stelt: 'Once an experimental drug is ready to be tested on people, it still has to be determined whether it can meet the many requirements to function as a medicine. For example, whether it is effective, whether it is safe, whether it is not broken down in the liver and what the best patient group is. Only one out of  twenty drugs that make it through this phase is ultimately suitable as a medicine.' Nowadays, there are many opportunities to find out at an earlier stage whether an experimental drug has clinical potential. This can save a lot of effort and money. 'Moreover, patients are not unnecessarily exposed to experimental drugs that do not work or are even toxic.'

Why only cancer drugs?

Why is Oncode-PACT specifically focused on cancer drugs? This is where the problem of inefficient drug development is greatest, explains Van der Stelt. 'Only 5% of the candidate drugs tested in humans are successful, compared with 10% to 14% for other diseases. This has to do with the fact that cancer differs strongly per individual and animal models are hardly predictive. Moreover, oncological research in the Netherlands is well organised in the form of the Oncode Institute.'

Major knowledge gaps

Over the next eight years, Oncode-PACT will build an infrastructure that brings together all the necessary knowledge and technology. All parties, from universities to large and small pharmaceutical companies, can go there if they want to research a potential cancer cure. 

Until now, there have been major gaps, Van der Stelt explains. 'The fundamental research of universities and academic hospitals provides all kinds of new  leads for medicines, but the knowledge to develop a medicine  with it is fragmented. Moreover, it is very expensive.' Oncode-PACT combines that knowledge and offers an integrated platform to make the process more efficient. 

Also a small company can gain access to all knowledge and infrastructure

Within Oncode-PACT, scientists from various disciplines will collaborate fully with each other as well as with companies. 'The process of developing a medicine is so expensive and risky that hardly anyone of our partners can do it alone. Within our consortium, academic groups or small companies, such as biotech start-ups, can submit an application. Even if they are not affiliated with Oncode-PACT. If it's promising, we provide the resources and infrastructure.'

And to the latest technologies

Those resources consist not only of money, but also of the latest academic insights and technologies to make medicine research more efficient. Such as: 

  • artificial intelligence;
  • mini tumours derived from patient tissue (organoids);
  • Activity-based protein profiling: a technique Van der Stelt is working on at the Leiden Institute of Chemistry (LIC). This enables researchers to detect potential side-effects of medicines in human cells or tissues at a very early stage; 
  • Techniques that lead to better interaction between drugs and their points of application in the body. This is the work of Laura Heitman, professor of Molecular Pharmacology at the Leiden Academic Centre for Drug Research (LACDR).

From virtual humans to electron microscopy

A promising development is artificial intelligence in medicine development. For example, Gerard van Westen, professor of AI and Medicinal Chemistry at the LACDR, is working on the development of a virtual human. This consists of algorithms that predict what an administered substance does in our body. Van Westen puts all the available knowledge about all the compounds ever studied into it, on which the model, i.e. the virtual person, tells how the draft drug will behave in our body. 

Designing more promising candidate drugs

Van Westen also uses artificial intelligence to design new, promising candidate drugs. These can then be produced and tested. Together with researchers from LIACS, the Leiden Institute for Advanced Computer Science, Oncode-PACT is developing new algorithms to improve and accelerate drug development. 

Another technique that is revolutionising drug development research, but is not yet accessible to everyone, is cryo-electron microscopy. 'This technique makes the structure of proteins on which drugs act, and how this happens, visible in detail. Such knowledge guides the design of new medicines. Oncode-PACT is investing in the Netherlands Centre for Electron Nanoscopy (NeCEN) to make this technology available to its network.'

This will create a well-oiled machine

As one of the leaders of Oncode-PACT, what will Van der Stelt do first? 'I will start to build a solid organisation with all the parties involved. In this way we can select the best projects and give them access to the entire network of knowledge, expertise and infrastructure within Oncode-PACT.' This will gradually create a well-oiled machine that brings new cancer medicines much closer, faster and more efficiently.

From molecule to stem cell cancer therapy: Oncode-PACT brings it closer

The Oncode-PACT consortium was partly created  in cooperation with the university-wide AI initiative SAILS, led by Joost Batenburg, professor of Imaging and Visualisation at LIACS. The consortium focuses on four research areas aimed at cancer drugs. These are molecules, antibodies, vaccines, and gene or stem cell therapies. Mario van der Stelt leads the molecules 'workstream'. The vaccine branch is also led by a Leiden scientist: Sjoerd van der Burg, professor of Immunotherapy. Van der Burg is group head of Experimental Cancer Immunology and Therapy at LUMC.

Within each of the four workstreams, the consortium aims to make optimal use of techniques in three areas: artificial intelligence, organoids (mini-tumours derived from patient tissue), and data from patient cohorts.

Leiden Early Drug Discovery & Development (LED3)

In the Science Faculty, researchers from several institutes, including LIC, LACDR and IBL, work together to improve drug development. They have united in the Leiden Early Drug Discovery & Development (LED3) network. Oncode-PACT is investing in the infrastructure of LED3, so that the researchers involved can further shape the latest developments and integrate them into anti-cancer drug research.

Text: Rianne Lindhout
Image above the article: Pixabay

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