PhD defence D. (Danny) Feijtel

Brief summary on the aim of the doctoral thesis:

Neuroendocrine tumors (NETs) often present in patients as metastatic disease. In this case the disease is largely non-curable. To target the metastases, radioactively labeled peptides that can bind to the tumor cells are injected in the bloodstream and irradiate the cancer from the inside: peptide receptor radionuclide therapy (PRRT). PRRT damages the DNA of the cancer cells and kills them. Unfortunately, not all cancer cells are killed and often the disease grows back. In order to improve the therapeutic outcome of NET patients we have mapped the radiobiological effects of PRRT on the tumor cells. We then used these data to find methods of sensitizing the NETs. We have studied the possibility of combining PRRT with the inhibition of DNA damage repair to increase therapeutic outcome. This does show promise, but does not always work and needs further investigation. To increase the anti-NET toolcase, we have investigated the function of a protein that is known to play an important role in the development of a proportion of NETs: menin. For the first time, we show that menin has an important function in the protection of the DNA and that loss of this proteins sensitizes the tumor cells to specific modes of DNA damage. Although the exact role of menin remains unclear, this information could potentially be used to treat menin-associated NETs in patients. It is our believe that the combination of these different layers of research might improve PRRT for NET patients in the future.