Homologous recombination deficiencies sensitise tumours to the hypoxia-activated prodrug CP-506, driving the development of a micro-CT imaging-based prediction model
Report on the International Wolfsberg Meeting on Molecular Radiation Biology/Oncology
Hurdal, Norway I 21-23 June 2025
by Lesley Schuitmaker, travel grant awardee
Attending the 17th International Wolfsberg Meeting on Molecular Radiation Biology/Oncology at Hurdalsjøen was a great experience. The beautiful location, combined with the relaxed and open atmosphere, made it easy to connect with and approach other researchers. What stood out to me most was how approachable and engaged everyone was, which led to many valuable conversations.
The programme included a variety of keynote lectures and proffered paper talks that covered a broad range of topics. I particularly enjoyed hearing about research outside my field of expertise, as this provided me with new ideas and perspectives that I can apply to our projects.
The social and interactive elements of the meetings were just as memorable as the scientific ones. One of the highlights was the “explain it to your Grandma” challenge, which took place during the infamous and ever-competitive Woslo Cup. In this challenge, each group had to explain a scientific concept in simple terms. Our group, focused on DNA repair, had to explain how radiation-induced damage to double-strand DNA occurs and how it is repaired. This challenge made me realise that even though we deal with these complex topics daily and they feel familiar to us, they can be quite difficult to grasp for those outside the field. It was a great reminder of how important it is to communicate our work in an accessible and relatable way. Plus, it was a fun and creative challenge that helped us to rethink concepts that aren’t usually easy to explain. It also created great team spirit, especially as the entire DNA repair group joined in.
Although my research is not directly focused on radiation biology, I gained more knowledge at this meeting about DNA damage and repair after exposure to different radiation types, such as proton and FLASH. Since our research is focused on targeting tumour hypoxia, I was especially interested in the talks and posters that addressed this topic. Several presentations and posters highlighted the use of different hypoxia PET tracers, oxygen-enhanced MRI, and 3D spheroid models that are transfected with hypoxia reporter vectors and that fluoresce under low-oxygen conditions. These approaches provided new insights that could be relevant for our work.
The variety of topics really added to the experience. Presentations ranged from the impact of sex differences in cancer cell lines on research outcomes to a more chemistry-focused invited talk on theragnostics.
During the meeting, I had the opportunity to present our latest research on the novel hypoxia-activated prodrug CP-506. We have been studying the role of DNA damage repair pathways in the therapeutic efficacy of CP-506. We have found that deficiencies in the Fanconi anemia, which are crucial in the repair of interstrand crosslinks, or the homologous recombination, which repairs double-strand breaks, pathways [A1] sensitised cancer cells and xenografts to CP-506. These findings suggest that patients with such DNA repair deficiencies could benefit most from treatment with CP-506, which is currently being evaluated in a phase I/IIa clinical trial. In addition, we have developed a radiomics-based foundation model, which can be used non-invasively to predict DNA damage deficiency from preclinical micro-CT scans of isogenic xenografts. As part of the ongoing clinical trial, we aim to test and optimise this foundation model on patient CT scans to assess its potential for future clinical applications
Presenting our work at the meeting gave me the chance to connect with others working on similar topics. These discussions were engaging and encouraging, and they reminded me of the value of sharing ideas in an open scientific setting.
Overall, the Wolfsberg meeting was an inspiring experience, filled with useful insights, meaningful connections, and engaging conversations. I am very grateful to the ESTRO biology committee for the travel award and would also like to thank the assessment committee and the meeting organisers for the opportunity to attend and present our latest research.
Lesley Schuitmaker
Department of Precision Medicine, GROW – Research Institute for Oncology and Reproduction, Maastricht University, The Netherlands
https://nl.linkedin.com/in/lesley-schuitmaker