Worldwide Cancer Challenge: The Riddle of the DNA Rings

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Prof. Dr. Anton Henssen © Charité | Wiebke Peitz

Paediatric oncologist Prof. Dr. Anton Henssen from Charité – Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), together with researchers from the USA and Great Britain, has been awarded a „Cancer Grand Challenge“: With almost 24 million euros, the international team will investigate the role of ring-shaped DNA in the development and fight against cancer. The Berlin team led by Prof. Henssen will receive more than one million euros for the next five years.

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In 2014, Prof. Henssen made an unusual discovery in the cells of children with cancer. He noticed that small rings of DNA had accumulated there. Part of the genetic information was thus no longer packed into the chromosomes as usual. And quite obviously, the rings were upsetting the rest of the genetic material in such a way that the children’s cells began to change. Since then, the topic has never left the 36-year-old researcher and physician, who has been leading the Emmy Noether Research Group „Genomic Instability in Childhood Tumours“ at the Experimental and Clinical Research Center (ECRC), a joint facility of Charité and MDC, since 2019.

„When I first became interested in circular DNA and its role in the development of cancer, I was pretty much alone in this,“ says Prof. Henssen. He is not only a scientist, but also looks after his little cancer patients as a paediatrician at the Clinic for Paediatrics with a focus on oncology and haematology at the Charité. In the meantime, however, the research field has moved further into the centre of scientific interest, says Prof. Henssen. For almost two years, the scientist and his project „CancerCirculome“ have been supported with a Starting Grant from the European Research Council (ERC).

The funding initiative „Cancer Grand Challenges“ – which since 2020 has been supported by the two largest funders of cancer research worldwide, Cancer Research UK and the National Cancer Institute of the National Institutes of Health in the USA – has not failed to notice the role of the tiny DNA rings, which until now has possibly been underestimated. She chose „extrachromosomal DNA“, or ecDNA for short, as one of nine grand challenges in cancer research. The Cancer Grand Challenges currently support more than 700 researchers and advocates in ten countries. Eleven teams are already taking on the most difficult challenges in cancer research – four new teams were announced on 16 June.

„It was clear to me that I wanted to take part in this challenge,“ says Prof. Henssen, who took up a Mildred Scheel Professorship of German Cancer Aid at the Charité on 1 June. Worldwide, there are only a handful of groups working on this topic. Now the team from the USA, Great Britain and Germany, led by Prof. Paul Mischel from Stanford Medicine in California, has received the award with its project „eDyNAmiC“ (extrachromosomal DNA in Cancer). This is associated with financial support of 20 million British pounds for the next five years. About one million of this will be available to Prof. Henssen and his Berlin team. It is now known that almost a third of all child and adult tumours carry DNA rings in their cells and that these tumours are almost always particularly aggressive, says Prof. Henssen. „We now want to find out what exactly makes these rings so dangerous, how they develop and how we can slow them down – in order to develop more effective therapies.“ This challenge is being taken up by the project team not only by biologists and physicians, but also by mathematicians and computer scientists.

Prof Henssen and his Berlin team, which also includes researchers from the Berlin Institute of Health at the Charité (BIH), first want to take a closer look at the structure of the rings and find out how their DNA is packaged in histones and other proteins and how the expression of their genes is regulated. „Because it is possible that changes in gene expression lead to tumours becoming resistant to currently available therapies with the help of the rings,“ he says. The fact that his once supposedly niche topic is now receiving such great attention and support naturally makes Prof. Henssen very happy. „Personally, nothing better could have happened to me,“ says the researcher. His great hope now is to help his patients in the foreseeable future who still have their lives ahead of them – thanks to a new type of therapy that attacks the rings and thus makes the deadly tumour disappear.

About the Charité – Universitätsmedizin Berlin

The Charité – Universitätsmedizin Berlin is one of the largest university hospitals in Europe with around 100 clinics and institutes on 4 campuses and 3,099 beds. Research, teaching and patient care are closely interlinked. With an average of 17,615 employees across Charité and an average of 20,921 employees across the Group, Berlin University Medicine is also one of the largest employers in the capital in 2021. Of these, 5,047 were employed in nursing, 4,988 in the scientific and medical fields and 1,265 in administration. Last year, 123,793 full and partial inpatient cases and 682,731 outpatient cases were treated at the Charité. In 2021, Charité generated total revenues of around 2.3 billion euros, including third-party funding revenues and investment grants. With 215.8 million euros in third-party funding received, Charité achieved another record in 2021. At one of the largest medical faculties in Germany, more than 9,000 students are trained in human medicine, dentistry, health sciences and nursing. In addition, 730 training places are offered in 11 health professions and 111 in 8 other professions. The Berlin University Medical Centre focuses on the following research areas: Infection, Inflammation and Immunity including research on COVID-19, Cardiovascular Research and Metabolism, Neurosciences, Oncology, Regenerative Therapies and Rare Diseases and Genetics. Scientists at Charité work, among other things, in 28 DFG Collaborative Research Centres, including seven with a spokesperson function, in three Clusters of Excellence, one of which has a spokesperson function, 10 Emmy Noether junior research groups, 14 grants from the European Research Council and 8 European collaborative projects with Charité coordination. Research at the Charité

Links:

Arbeitsgruppe von Prof. Dr. Anton Henssen am ECRC
Der DNA-Künstler – Porträt Prof. Dr. Anton Henssen
Doppelt ausgezeichnet: Berliner Wissenschaftspreis für zwei Charité-Forscher (Pressemitteilung vom 23.7.2021)
Dem Ursprung und Wirken zirkulärer DNA auf der Spur (Pressemitteilung zum ERC Starting Grant vom 3.9.2020)

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