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Interview Jarno Drost: Unravelling the molecular landscape of childhood cancers

Jarno Drost is an Oncode Investigator and a PI at the Princess Máxima Center. His work focuses on unraveling the biology of childhood solid tumors, looking to understand how these tumors develop and how current technology can be used to help patients. He recently won the Career Development Award from the AACR and St. Baldrick’s Foundation. But he didn’t always dream of a career in research.

What makes your work interesting? 

In the past years I did my PhD at the Netherlands Cancer Institute (NKI) and my postdoc at the Hubrecht Institute, focusing on adult cancer. The general perception is that cancer is an age-related disease. But, unfortunately, also children get cancer. Childhood cancer develops in fundamentally different way than adult cancer.  We try to figure out how it is possible that very young children can get cancer. That makes it both meaningful and scientifically fascinating.

How is cancer in children different? 

Adult cancer is thought to develop because of sequential accumulation of mutations. Over the years, cells accumulate more and more DNA faults. Now and then, faults occur in cancer-related genes, ultimately resulting in unrestricted growth. This is also why tumors in adults typically contain hundreds to thousands of DNA faults.

Children simply did not have the time to accumulate so many faults in their DNA and therefore childhood cancers are genetically much simpler than adult cancers, with much fewer mutations. In fact, for some childhood tumors only a single recurrent genetic driver has been identified. This seems particularly true for tumors in very young children, so-called embryonal tumors. In a substantial number of cases, a mutation is already present right from fertilization, or occurs very early in embryonic development.

Why is that?

It is typically a developmental process that goes awry as a consequence of such a genetic change. For instance, a very early kidney progenitor cell is supposed to develop into an entire kidney. To do so, the cell must initially multiply very quickly. At a certain point these cells have to stop multiplying and separate into different types of cells needed in the kidney. Some genetic changes take the brakes off the cells’ growth.

Remarkably, quite a few childhood solid tumors look like fetal tissues. Wilms’ tumor, a type of kidney cancer, is perhaps the most striking example. Even though the genetic drivers of childhood tumors seem to be relatively simple, the developmental processes involved are very complex and dynamic. This is even further complicated by the fact that we still do not understand many aspects of normal embryo formation. All this makes it challenging to pinpoint what kind of process are involved in malignant growth and to find good targets for therapy.

Why did you decide to make the switch – from researching cancer in adults to children? 

During my postdoc, I realized that it was probably better to change research area to be able to really develop an independent research niche. When I got the opportunity to join the Princess Máxima Center, I did not have to think very long.

I realized that in pediatric oncology, use of organoid technology, which I extensively worked with in my time as postdoc in the Clevers lab, was still relatively in its infancy. So I figured I could contribute something unique to this field by building organoid models for childhood cancers and using such models for both fundamental and more translational research projects.

A second reason is a more emotional one. I think everybody agrees that a child with cancer is just terrible. Even though survival has increased substantially, survivors have to deal with severe side effects caused by the intense treatment. The mission of the Máxima, ‘curing every child with cancer with optimal quality of life’ appealed to me and is something I just really want to contribute to.

Does this topic weigh on you?

It is of course very confronting to see these very sick children in our institute every day. It does make me realize though how lucky I am that my children are healthy. It is of course horrible for anyone, child or adult, to get cancer. But when children get it, it seems even worse. They have not done anything that could have increased the risk of developing cancer such as smoking or sunbathing for hours on end. Some of these children already developed a tumor when they are born, which just seems unfair.

How do you cope with that?

It makes me even more motivated. In my lab, we make use of patient derived materials. That makes our research very tangible. In some cases, we even meet parents whose child passed away and we received material for our research. Although confronting, this just really makes me want to contribute to the mission of the Máxima even more.

If we imagine your retiring party, many years from now - what would you like people to say about you?

I am still a relative newcomer in the pediatric oncology field. So the first thing I want to accomplish is that the people in this field acknowledge that I am really contributing something unique and useful. It is not easy as a young PI to start working in a field where essentially no one is familiar with your previous work and a network has to be build up from scratch again.

My group was one of the first to make use of organoids in pediatric cancer research. Introducing such new cell models means that I here and there broke with the standards in the field which were build up by experts over decades. Receiving the award from AACR/St. Baldricks foundation is a very nice first indication that the international community likes our contributions to the field.

That means having your findings turned into clinical solutions…

Yes. I primarily do basic research, but this can lead to important clinical implementations. And this is what I, amongst others, like about being part of Oncode. The community and the dedicated support teams really helps us, Oncode Investigators, to find opportunities to implement our scientific findings in the clinic. For instance, Oncode is helping me to initiate collaborations with industrial partners to find opportunities to bring a novel drug my lab identified for the treatment of an aggressive childhood tumor to the clinic. Because of such efforts, being part of Oncode allows me to reach my ultimate goal – that my research will really contribute something to society.

This interview appeared in the December issue of Oncode's digital magazine.