PhD defence T. (Tim) Heemskerk

Below is a brief summary of the dissertation:

Proton therapy is a relatively new form of radiotherapy for cancer treatment. Unlike conventional photon-based radiation, protons release their maximum energy at a specific point (the Bragg peak), allowing for better sparing of surrounding healthy tissue. This makes proton therapy particularly suitable for tumors near sensitive organs and for use in children.

Although proton therapy is generally assigned a fixed relative biological effectiveness (RBE) of 1.1, this value can vary depending on factors such as the type of DNA damage and a cell’s ability to repair it. This thesis investigates how cells detect and repair DNA damage caused by protons, and which repair mechanisms are involved.

We studied how cells respond to different types of DNA damage and how two major repair pathways—NHEJ and HR—interact. We also examined how heating cells (hyperthermia) affects their sensitivity to protons, and how LET (a measure of energy deposition) influences the severity of DNA damage.

In addition, we developed new techniques to visualize DNA repair live during and after irradiation, and created a method to precisely irradiate small tumors in animal models using protons. Finally, we tested whether our laboratory findings also apply in mouse tumor models.

This research contributes to a better understanding of the biological effects of proton therapy and supports the development of more effective and targeted cancer treatment strategies.