Identifying Novel Combination Therapies for Proton Treatment of Glioblastoma

The Project

Proton therapy for cancer was recently introduced in Norway, with the first patient treated at the proton facility at Oslo University Hospital in 2025. Compared with conventional X-ray radiotherapy, proton therapy enables more precise radiation delivery to the tumour, thereby reducing radiation exposure to surrounding healthy tissue. However, despite its increasing clinical use, the biological effects of proton radiation on cancer cells remain incompletely understood.

Proton radiation produces a higher ionisation density than X-rays, resulting in more complex and clustered DNA damage. Consequently, tumour cells may activate different DNA damage signalling pathways and DNA repair mechanisms following proton irradiation compared with conventional radiotherapy. Understanding these differences could open new opportunities to develop more effective and personalized cancer treatments.

To identify targets for proton-based combination therapy, our research group has performed a large-scale screen of more than 2,000 compounds, revealing inhibitors of DNA repair and cell cycle checkpoint activation. This screen identified several promising candidate drugs that show differential responses when combined with proton versus X-ray irradiation. These findings provide an exciting starting point for investigating new strategies to enhance the effectiveness of proton therapy.

This project focuses on glioblastoma, the most common and aggressive primary brain tumour in adults. Despite intensive treatment, prognosis remains poor and there is an urgent need for improved therapeutic approaches. By identifying drugs that preferentially enhance the effects of proton irradiation, this project may contribute to the development of novel treatment strategies for glioblastoma patients.

Project Aims

The overall goal is to validate and characterize promising drug candidates identified in our screening studies and investigate their interaction with proton radiation in glioblastoma cells.

The specific aims are:

  1. Validate promising candidate drugs by assessing their effects in combination with proton versus X-ray irradiation in patient-derived glioblastoma cell models.
  2. Characterize cellular responses by investigating DNA repair pathway activation and cell cycle checkpoint regulation following combination treatment.
  3. Explore underlying mechanisms for selected candidates to identify molecular pathways responsible for their differential responses to proton and X-ray radiation (time permitting).

Methods

The project will involve a broad range of experimental techniques, including human cell culturing of established and patient-derived glioblastoma lines, cell survival assays, flow cytometry analysis, Western blotting, immunofluorescence microscopy, and proton and X-ray irradiation of cells. The student will gain hands-on experience in experimental design, data analysis, and interpretation of results.

Why This Project?

This project offers a unique opportunity to contribute to research linked directly to Norway's newly established proton therapy facilities, addressing important questions with potential clinical relevance. The student will become part of a research group working at the interface between molecular cancer biology, radiation research, and translational cancer research. The results will improve our understanding of how proton therapy affects cancer cells and may provide a basis for developing novel proton-based combination strategies for glioblastoma treatment.

Who We Are Looking For

The ideal candidate is curious, analytical, dedicated, and able to work both independently and as part of a team. A strong commitment to the project and enthusiasm for laboratory-based research are highly desirable.

We offer:

  • A friendly and supportive research environment
  • Close scientific supervision
  • Training in advanced laboratory techniques
  • Participation in cutting-edge cancer research
  • An opportunity to contribute to research with potential impact on future cancer treatment

Supervisors:

Main supervisor: Randi G. Syljuåsen, PhD (Group Leader), ransyl@ous-hf.no

Co-supervisor: Linn H. Steive, MRes (PhD Student), lsteiv@ous-hf.no

Internal supervisor: Pål Falnes (IBV)

Research group:

Radiation Biology and DNA damage signaling

Department of Radiation Biology

Institute for Cancer Research

Norwegian Radium Hospital

Oslo University Hospital

Ullernchausseen 70, 0379 Oslo

http://www.ous-research.no/syljuasen/

Publisert 13. aug. 2026 11:03 - Sist endret 13. aug. 2026 14:05

Omfang (studiepoeng)

60