Ten years of Hartwig Medical Foundation: a retrospect and a glimpse of the future  

In its first decade, Hartwig Medical Foundation has made significant progress towards its goal of providing access to all diagnostic information on patients with cancer as a foundation for treatment. Director Hans van Snellenberg looks back on those first ten years. Together with Dr. Hilde Nienhuis, medical oncologist at UMC Utrecht and Medical Team Lead at Hartwig, he also takes a look ahead at the goals the foundation wants to achieve in the coming years. 
 

Frank van Wijck, science journalist  

It was Emile Voest, a Professor of Medical Oncology at the Netherlands Cancer Institute in Amsterdam, who, with his ideas on comprehensive data analysis and sequencing as the foundation for precision medicine, initiated the establishment of Hartwig Medical Foundation. Together with Professor of Human Genetics Edwin Cuppen (UMC Utrecht), he carried out a study at the Center for Personalized Cancer Treatment (CPCT). “The idea was that by generating a lot of genetic patient data, it would be possible to recognize patterns, and these could be used to predict whether or not a patient would respond to a treatment,” explains Hans van Snellenberg.  

“In 2014, philanthropist Rob Defares offered to provide funding to establish Hartwig, and asked them a pertinent question: Can you write a business plan for a professional sequencing center which will ensure rapid growth of the database?” 

 
Of the initial investment of thirty million euros, ten million went to the Illumina Hi Seq X 10 sequencing platform. “We purchased ten devices with a combined capacity for 5,000 patients a year,” Van Snellenberg says. “A year and a half later, we made the leap from 12 to 44 participating hospitals and the collection of data from 3,000 patients per year. Today, our genetic database is the largest of its kind in the world, with WGS data of over 7,000 patients, and contains clinical data,  and treatment information and outcomes. We know that many expensive therapies are useful only in a minority of patients. If you know in advance which patients will and will not benefit from a treatment, you can treat only those patients who are likely to respond, and so decrease the costs. In addition, you can save patients from the side effects of ineffective treatments. Currently, we are throwing one and a half billion euros a year down the drain. Collecting clinical and outcome data provides a tool to change that.” 

First reactions 
Not all hospitals were enthusiastic about Hartwig, Van Snellenberg admits. “Some of them immediately embraced our principles, such as Erasmus MC. But others wondered who those cowboys from Amsterdam were, and whether the results from whole genome sequencing (WGS) were reliable. To bridge the gap with the clinical world, we were joined by Dr. Paul Roepman, a clinical molecular biologist in pathology. What also helped to win trust was the WIDE study, conducted jointly with the Netherlands Cancer Institute. With this study, we showed that we could achieve the same molecular test results with WGS as all other individual tests combined. This proved the clinical value of WGS.” 
The data in the database led to improvements in molecular diagnostics. “An example is the diagnosis of cancer of unknown primary (CUP),” explains Van Snellenberg. “Together with pathologists and software developers, and based on the database, we developed the CUPPA algorithm to predict the primary tumor type. This has demonstrated the clinical benefit of broad testing, including for these CUP patients, and this diagnostic procedure is now covered by health insurance.” 
 

Partnerships 
Various partnerships have since been established, not only with academic and peripheral hospitals, but also with services like GenomeScan. “A logical partnership,” says Van Snellenberg, “because we both sequence and have the same infrastructure. The difference is that GenomeScan specialized in clinical genetics, and we in oncology. Together, we are accelerating the development of affordable diagnostics based on WGS.” 
Another example is the international collaboration with The Jackson Laboratory’s Clinical Knowledgebase (CKB). “They analyze 20,000 scientific publications every year,” says Hilde Nienhuis. “We use the CKB to refer to appropriate treatments and clinical trials in our WGS reports. The important next step is to further tailor this knowledgebase to the Dutch situation, so that we can specify which treatments are available to patients in the Netherlands.” 

Building bridges 
Nienhuis has been Hartwig’s Medical Team Lead since 2022. “The combination with my work in patient care at UMC Utrecht has been hugely beneficial for me,” she says. “I can bridge the gap between clinical practice, the laboratory and software development, which are traditionally separate worlds. In the medical team, we work with two clinical molecular biologists in pathology. We carry out the final check of the WGS report, which is automatically generated based on the sequencing and analysis software. We also have a physician-researcher who works in the field of GENAYA, which allows us to fully map the DNA of a thousand young adults with cancer. We now have agreements with 34 hospitals to implement WGS. We want to know why young people get cancer and we are seeking clues that can lead to their treatment. This is another gap bridged, because GENAYA is a theme I am also involved with in the clinic.” 

 
“You are our link to the users,” says Van Snellenberg. “Suppose there is new evidence for a specific marker. We need to be able to promptly modify our software to demonstrate that the patient benefits from treatment. So, Hilde is there to funnel all new insights to our software developers, ensuring that our reports always reflect the latest scientific literature.” 

The future 
Two dominant developments will have to be taken into account in the next few years, says Van Snellenberg: staffing shortages and the cost of care. “Our first goal was to improve care, but these two themes have since become just as critical,” he says. “We have now pretty much reached the point where WGS is no more expensive than standard diagnostic procedures. And we are well on the way to demonstrating that a new sequencing platform will further reduce the cost price. If we can implement this platform, a WGS test will become a thousand euros cheaper.” 

Van Snellenberg continues: “In addition, we want to add more value for physicians. We are doing this with the ACTIN algorithm, which automatically produces an overview of suitable trials for patients with metastatic cancer. We are also engaged in research to be able to predict, based on real-world data, whether and how long a patient will benefit from a drug. We are using data from the Netherlands Cancer Registry (NCR) and the PLCRC cohort on colorectal cancer, among others, to determine whether this is feasible.” 

 “We still lack a lot of the clinical data we need to be able to properly answer research and clinical questions,” continues Nienhuis. “We already use the NCR data for GENAYA, and we want to take the next step together with the Netherlands Comprehensive Cancer Organisation (IKNL). This involves carrying out care evaluations to predict more accurately which patients will or will not benefit from a given therapy. To do this, we need to bring together multiple data sources in collaboration with various other parties in the Netherlands. Again, in close cooperation with IKNL.” 

And internationally, too, Van Snellenberg adds. “Germany, for example, has a cohort of 4,000 patients with rare types of cancer. Genomics England also has a valuable cohort. And at the Clinical Cancer Genomics 2025 conference in March, we will try to take data sharing further in a collaboration with six European parties. We want to be ready in time for the European Health Data Space.” 
 

From: Oncology Up-to-date 2025 vol. 16 issue 1