Treatment of head-and-neck squamous cell carcinoma (HNSCC) by targeting hypoxia-associated therapy resistance
Awarded poster at the 17th International Wolfsberg Meeting on Molecular Radiation Biology/Oncology
By Danny Knobloch-Sperlich, travel grant awardee
Taking part in the Wolfsberg meeting was an important experience for me. Above all, it provided scientific inspiration and opportunities for professional exchange. The conference was exceptionally well-organised, with a well-balanced programme and an inviting atmosphere that encouraged discussion across disciplines and career stages. The familiar setting of the Wolfsberg estate fostered focused interactions, and I greatly appreciated the chance to connect with colleagues from different research areas in radiation biology. I particularly enjoyed this mix of scientific exchange and sociable experiences during meals, sports and games, especially the WOslo Cup, which was great fun due to the combination of activity and creativity.
Among the many excellent sessions, session 3 on the tumour microenvironment stood out as particularly relevant. This topic lies at the core of my research, and the presentations and discussions within this session addressed the most pressing questions in our field, namely, how hypoxia, metabolic adaptation, and cellular signalling contribute to therapy resistance in solid tumours. The speakers provided new insights into mechanisms by which the microenvironment supports tumour survival and progression, as well as potential ways to disrupt these pathways therapeutically. I found it particularly inspiring to see how different research groups are approaching the challenge of therapy resistance from different angles, which include immunology, metabolism, and hypoxia-targeted therapies.
This thematic focus closely mirrored my current research, which is intended to improve the treatment of HNSCC by targeting hypoxia-associated therapy resistance. Specifically, our working group is researching novel substances, betulin-carbonic anhydrase inhibitor (CAI) conjugates, to improve the irradiation of radioresistant (hypoxic) tumours in particular. Betulinic acid is a natural substance from birch bark, which has a selective effect on tumours. It has been coupled with CAIs, which inhibit hypoxia-induced carbonic anhydrase IX (CA IX) in particular. In HNSCC, CA IX is frequently overexpressed and correlates with a poor prognosis. My project aims to sensitise hypoxic tumour cells selectively towards radiation. For this purpose, I developed two coloured HNSCC spheroid models, with which the radiosensitivity of normoxic and hypoxic cells could be analysed separately. In my investigations, I was able to demonstrate in both 2D and 3D HNSCC models that betulin sulphonamide conjugate 9 (BSC 9) improves the effects of irradiation, particularly under hypoxia. In addition to cytotoxicity and radiosensitivity, I performed RNA sequencing analyses and investigated various cell and radiobiological effects that were induced by BSC 9.
The implications of this work are twofold. First, BSC 9 shows promise as a dual-function agent that combines intrinsic cytotoxicity with hypoxia-selective radiosensitisation. Second, the study supports a broader strategy of targeting metabolic and enzymatic adaptations within the tumour microenvironment to improve therapy outcomes. The feedback I received during the poster session at the Wolfsberg meeting, including questions about possible translational pathways and combination strategies, was invaluable for further developing my work.
In conclusion, the Wolfsberg meeting not only deepened my understanding of the tumour microenvironment but also helped me to position my research within a wider scientific and translational context. I am proud to have received the ESTRO travel grant. It shows that my research is important and is recognised internationally. I have returned to my university with renewed motivation and valuable input for the next steps of my project.
Danny Knobloch-Sperlich
Department of Radiotherapy
Martin Luther University Halle-Wittenberg
Ernst-Grube-Straße 40
Halle (Saale), Germany
LinkedIn: linkedin.com/in/danny-knobloch-206b14249