Targeting DNA repair to enhance radiosensitivity in proton therapy

The project

Proton therapy for cancer was recently introduced in Norway, with the first facility opening at Oslo University Hospital, Radiumhospitalet, in March this year. In our team we are very excited to launch preclinical research projects focused on understanding how to fully utilize the potential of proton therapy. 

Compared to X-rays, which are used in traditional radiotherapy, proton therapy delivers radiation to tumors with greater precision, thereby minimizing damage to surrounding healthy tissue. However, the biological effects of protons on tumor cells are still not fully understood. In particular, protons generate a higher ionization density than X-rays, leading to more complex and clustered DNA damage. These distinct damage patterns activate unique DNA repair mechanisms that remain poorly characterized and are not yet fully exploited for therapeutic benefit. 

The goal of this project is to evaluate the effects of DNA repair inhibitors in combination with proton radiation in lung cancer cells. Lung cancer remains the most lethal cancer worldwide, and proton therapy-based combination therapies could provide new therapeutic avenues. The specific aims are: 

  1. To assess the effects of eight DNA repair inhibitors—targeting different repair pathways—in combination with proton versus X-ray irradiation, using high-throughput cell viability assays in lung cancer cells. 

  1. To characterize the differential activation of DNA repair pathways following proton and X-ray radiation. 

  1. To elucidate the molecular mechanisms underlying the differential radiosensitization observed with one or two selected DNA repair inhibitors.  

Various laboratory methods will be used, including human cell culturing, robotic handling, cell survival assays, Western blotting, flow cytometry analysis, immunofluorescence microscopy, and proton and X-ray irradiation of cells. The project results will deepen our understanding of the biological effects of proton therapy and may identify novel combinations of proton irradiation and DNA repair inhibitors that could improve future lung cancer treatments. 

We are seeking a highly motivated master student who is interested in an exciting project in molecular cancer research. It is advantageous to have a good analytical understanding and the ability to work independently and accurately. We provide a friendly and stimulating working environment. 

Contact information

Main supervisor: Randi G. Sylju?sen PhD (Group leader),?randi.syljuasen@ous-hf.no, 22781468 


Co-supervisor: Sissel Hauge PhD (Scientist),?sissel.hauge@ous-hf.no  

Group for Radiation biology and DNA damage signaling 
Department of Radiation Biology 
Institute for Cancer Research 
Norwegian Radium Hospital/ Oslo University Hospital 
Ullernchausseen 70 
N-0379 Oslo 
???????http://www.ous-research.no/syljuasen/ 

 

Publisert 11. aug. 2025 08:27 - Sist endret 11. aug. 2025 08:27

Veileder(e)

Omfang (studiepoeng)

60