Investigating the role of the Keap1-Nrf2 pathway for FLASH Radiation – Can activation/deactivation of Keap1 enhance the FLASH effect?
FLASH radiation is a novel radiotherapy technique that shows great potential in improving cancer treatment. However, very little is known about the biological mechanisms behind the highly beneficial FLASH effect. The newly created research group "Physics and Biology of FLASH Radiation" at the Oxford Institute for Radiation Oncology aims to identify these mechanisms, explain the effect, and to find the optimal way of implementing the technique in clinical practice. A major hypothesis to explain the FLASH effect is that less reactive oxygen species (ROS) are created following FLASH irradiation compared to conventional dose rate irradiation. The Keap1-Nrf2 pathway is a crucial regulator of oxidative stress (i.e. excess of ROS) in the cell and alterations of this pathway can alter the effect of conventional radiotherapy in cancer treatment. In this DPhil/PhD project, using state-of-the-art techniques, you will investigate if manipulation of this pathway through molecularly targeted therapies can further enhance the FLASH effect.
FLASH radiation is a novel radiotherapy technique that show great potential in improving cancer treatment. However, very little is known about the biological mechanisms behind the highly beneficial FLASH effect. Our research group aims to identify these mechanisms, explain the effect, and to find the optimal way of implementing the technique in clinical practice. We have a linear accelerator dedicated to preclinical research, which is capable of delivering conventional as well as ultra-high dose rate irradiation, i.e. FLASH irradiation.
- JD. Wilson, EM. Hammond, GS. Higgins, K. Petersson. “Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?” Front. Oncol. 9, 1563 (2020). 10.3389/fonc.2019.01563
- G Adrian, E Konradsson, M Lempart, S Bäck, C Ceberg, K Petersson. “The FLASH effect depends on oxygen concentration” The British Journal of Radiology, 93, 1106 (2020). 10.1259/bjr.20190702
- P. Montay-Gruel*, K. Petersson*, M. Jaccard, G. Boivin, J.F. Germond, B. Petit, R. Doenlen, V. Favaudon, F. Bochud, C. Bailat, J. Bourhis, M.C. Vozenin, “Irradiation in a Flash: Unique Sparing of Spatial Memory in mice after Whole Brain Irradiation with dose rates above 100 Gy/s.” Radiother Oncol 124, 365-369 (2017). *Equal contribution. 10.1016/j.radonc.2017.05.003