|Institution:||Universiteit van Amsterdam|
|Full text PDF:||http://hdl.handle.net/11245/1.540412|
This thesis discusses the two contrasting sides of radiotherapy: tumor control and normal tissue toxicity. On one hand, radiation treatment aims to target the tumor with the highest possible radiation dose, inducing as much lethal DNA damage as possible. On the other hand however, escalation of the radiation dose will also result in an increase of normal tissue damage and hence of the normal tissue complication rate. Unfortunately, ionizing radiation cannot distinguish cancer cells from normal, healthy cells and damages all cells in the irradiated area. Fractionation of the total radiation dose to allow time for normal cells to repair together with high precision image-guided technologies to minimize the irradiated normal tissue volume, already augmented the utility of radiotherapy significantly. However, Improvements in radiotherapy remain necessary as several tumors are still poorly controlled by radiation alone and on the other hand, increased tumor control and subsequent survival rates make also the quality of life in cancer survivors more en more important. Exploring the molecular events after radiation treatment, in cancer cells and in normal cells, might unravel mechanistic insides and might lead to the identification of new therapeutic targets or biomarkers. In the studies described in this thesis, the molecular events involved in the repair of radiation induced DNA damage are investigated. By interfering with DNA double strand break repair processes, we aim to sensitize tumors and cancer cells to ionizing radiation and we measured the activity of these processes to predict tumor sensitivity and normal tissue toxicity.