PhD Defence Jurrian de Kanter

Cancer treatment has become more effective over the past seven decades. This is certainly the case with children with cancer. Where seventy years ago only 10% of children with cancer survived, it is now more than 80%. 

Chemotherapy, radiotherapy (radiation) and surgery are the most common treatments for cancer. Children can tolerate higher doses of chemotherapy. This allows cancer cells to be killed better. This is one reason why children heal from cancer more often than adults.The high dose of chemotherapy given to children has a downside. Chemotherapy and also radiotherapy damage the DNA of cells. This happens not only in cancer cells, but also in healthy cells. DNA damage in healthy cells can cause acute side effects, such as hair loss due to the death of cells in the hair follicles. Many long-term side effects also occur. Such side effects are called "late effects" and can occur and/or persist years to decades after cancer treatment.

This dissertation described molecular studies that identified chemotherapy drugs and nucleotide analogs that damage the DNA of healthy cells, and described genes that may be potential new targets for developing less harmful therapies. This study and others like it improve our understanding of the harmfulness of cancer therapy and can be used to effectively design future clinical trials that aim to reduce late effects in children with cancer. These could include developing or testing less harmful therapies or reducing the dose of, for example, platinum-containing drugs or ganciclovir.