Miriam: “Several new cancer drugs have been developed over the past few years, particularly in immunotherapy. This has broadened the treatment options for cancer patients, including in my area of expertise: colorectal cancer. From only three drugs 15 years ago, there are now nine possible drugs available for my patients. This includes the drug Pembrolizumab, which was invented by Dutch scientists.” 

Hans: “The level of cancer research in the Netherlands is very high. We are one of the top three world’s best performing countries when it comes to biomedical science, thereby outperforming, for instance, the United States and China. Given that we are only a tiny country, this is a huge achievement.” 

Miriam Koopman, medical oncologist (UMC Utrecht).

Hans: “It can be complicated for scientists to get pharmaceutical companies to work with their discoveries, even when these are promising. At the same time, developing a drug within the walls of a research institute is currently beyond scientists’ capacity, experience and budget. One way to go around that process is to set up your own start-up but not every scientist has the means or the will to do so. This is one reason why the creation of Oncode was so important, to forge more bridges between the world of science and the world of pharma.” 
 
Miriam: “As a physician, I see phase 3 clinical trials as a major bottleneck. This is the last clinical trial, during which a drug’s effectiveness is tested on hundreds or thousands of patients. For one thing, the failure rate of phase 3 trials is very high; only a minority of the tested medicines can pass this round. As a result, a lot of time and money invested in the creation and testing of the drug are wasted.” 
 
“But that’s not all. The ways in which phase 3 trials tend to be organized are problematic. Elegibility criteria are often very strict. Only around 5% of cancer patients are being treated within clinical trials. These patients tend to be relatively young and fit, unlike your average cancer patient. This means that the guidelines of new medicines entering the market, and which I should follow as a doctor, do not necessarily fit the needs and vulnerabilities of my patients.” 

Miriam: “Out of my frustration over the lack of inclusion of elderly and unfit patients in trials, I initiated the Prospective National CRC cohort study, in which various scientists carry out longitudinal research into colorectal cancer. Any patient can join, including patients that are eighty years old or over. There is an infrastructure for the collection of clinical data, patient-reported outcomes and the storage of blood and tumor tissue from patients with small bowel, colon, rectal and anal cancer. This is all done after obtaining the patient's consent.” 
 
“We have been running for eight years now, but it’s already clear this project answers a great need. Nearly all Dutch hospitals participate, while over 13,000 patients consented to participate. This has given research into colorectal cancer a boost. Currently, there are twenty ongoing sub-studies. But that’s not all: there have been interventional trials and we were able to add new, relevant data to the registration process for new drugs approved by the European Medical Agency.”

“Also, we are currently looking into a tiny subgroup of colorectal cancer patients to see if they can be helped by trying a certain new drug which was approved, but not yet used because the number of patients for whom it can be used is so low. And there are five trials up and running regarding the predictive role of circulating tumor DNA in blood, to decide if certain groups of patients need chemo after surgery or not. In the long run, patients and their doctors could also use the system to check what treatments benefited patients with a similar tumour type as theirs, to decide upon the best treatment.”

Hans: “I feel I have been able to make significant changes in the way preclinical research can be carried out thanks to the organoid technology I have been able to help develop. Alongside key discoveries in Artificial Intelligence, this has revolutionized testing in the lab. By growing organoids based on human cell tissue, we no longer depend on tests on mice or other animal to tests prospective medicines in the lab and can see quicker what these can do in the human body. This has made for more realistic modelling, which can help pharmaceuticals optimize their clinical trials.”

Hans Clevers, molecular biologist and Oncode Investigator (UMC Utrecht, Hubrecht Institute and Princess Máxima Center for Pediatric Oncology).

Hans: “I agree. Information is very scattered throughout the system due to bureaucratic barriers between the actors involved, such as universities, hospitals, government agencies, pharmaceutical companies and so on. This can even be the case between public and semi-public actors, or within certain organisations. There needs to be much more knowledge transfer throughout the system, to boost efficiency in the cancer medicine development chain. Now precious knowledge is often lost when one actor takes over from another.”  
 
Miriam: “I believe it’s essential to create a national health infrastructure with data accessible to everyone in the cancer drug development chain. As the PLCRC initiative shows, patients’ data are highly relevant to learn and improve treatments for the next patient, from toxicity and lab results to quality-of-life questions. If all the stakeholders in cancer drug development would have access to these datasets and where possible complement these, many issues could be answered much faster than in the current system, where actors tend to have their own isolated datasets and less access to comprehensive patient data. Such a system could also change the status of patients. Rather than being mere passive recipients at the end of the cancer medicine production chain, patients as a group could actively contribute and even steer cancer drug development.” 
 
Hans: “Getting access to a massive amount of patient data, could indeed be revolutionary. It would give lab tests a great boost in the preclinical stage. With the progress in organoid technology, we could use blood and cell tissue from patients to grow tumor tissue. Combined with great advances in Artificial Intelligence and molecular testing, this would allow scientists to thoroughly study the impact of a certain cancer medicine in the lab, including upon many different subtypes of tumors. This greatly enhances insights into the workability of a medicine, as well as its potential toxicity and other negative side effects at a much earlier stage. Meaning that by the time a medicine would be clinically tested, it would stand a far higher chance of success.” 

Hans: “It’s our smallness that gives us an edge. It makes coordination and connecting key actors easier. Also, we already have a very well-organized healthcare system, in which there are already many linkages between actors.” 

“Moreover, past events show that there is a willingness among key stakeholders in cancer drug research to collaborate.  The creation of Oncode Institute is a prime example. But also, a national institute like the Princess Máxima Center shows an ability to cross borders to work together, involving oncologists, patient organisations, hospitals and ministries. And of course, we already have a national cancer registry system in place. Together with the Scandinavian countries we are forerunners in that respect.” 

Miriam: “I agree. It is perhaps also telling that many of the publications on real world data come from the Netherlands. So perhaps we should turn it around: if there is one country that could pull this off, that is the Netherlands.”  

Oncode-PACT Growth Fund (Groeifonds) proposal 
Last year, together with many consortium partners, Oncode Institute submitted the Oncode-PACT (Preclinical Accelerator for Cancer Treatments) proposal to the Growth Fund Commission. This proposal addresses many challenges that are mentioned in this interview. Hans Clevers and Miriam Koopman are part of the PACT consortium. The goal of Oncode-PACT is to bring together and build out the state-of-the-art drug development infrastructure, make it easily accessible and to innovate the drug development process itself. By building early validation and de-risking into the drug development pipeline, our approach should result in higher chances of success. Read more about this on our website

Hans Clevers

As of March 18, 2022, Hans Clevers will head Roche’s Pharmaceutical Research and Early Development in Switzerland, to lead research into the development of drugs for a wide variety of diseases while also joining its Corporate Executive Committee. Hans will stay closely connected to the Oncode research community and continue to be involved with the Hubrecht Institute and Princess Máxima Center as an advisor/guest researcher.

Credits: interview by Marloes van Amerom; photography by Marloes Verweij, Laloes Fotografie