Specialization
Hyperthermia and radiobiology
Focus of research
1) Enhancing radiotherapy or chemotherapy with DNA repair inhibiting agents, such as hyperthermia and PARP1-inhibitors. In the laboratory these sensitization effects are investigated and potential new treatment combinations are tested, both in cell lines and animal experiments. Hyperthermia is a local treatment, in which the tumour is heated up to 41- 43 C for approximately one hour. As a cancer treatment, hyperthermia should always be combined with either radiotherapy of chemotherapy; as a single therapy, hyperthermia is not effective in treating cancer. This is due to the fact that both radiotherapy (ionizing radiation) and chemotherapy induce DNA lesions. The most severe lesions are DNA double strand breaks (DSB). These DSB are repaired by two major repair pathways, Non-Homologous end-joining (NHEJ) and Homologous Recombination repair (HR). Hyperthermia treatment of 1 h at 42 C can inhibit the HR repair via a transient degradation of the BRCA2 protein which one of the major proteins of this pathway. In the laboratory we investigate the biological effects of hyperthermia in in vitro cell cultures. One of the research topics is the study of the DNA damage repair pathway. DNA repair proteins that accumulate at the sites of the DSB are studied with fluorescently labelled antibodies and studied with the fluorescence microscope.
2) In our laboratory we also study the effects of hyperthermia (in combination treatments) on tumours infected with the human papillomavirus (HPV). From clinical studies it is known that hyperthermia is very effective on cervical cancers, of which almost all tumours are infected with HPV. In our laboratory we found that hyperthermia can disrupt the interaction between the HPV-protein E6 and tumor suppressor protein p53, which causes activite p53 resulting in more cell kill. More recently, we investigated the effects of combination treatments of radiotherapy or chemotherapy with hyperthermia and immune checkpoint inhibitors on the effectiveness on the primary tumour growth and on distant metastases (in animal models).
3) Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is used to treat peritoneal metastases of colon cancer. In our laboratory we are focussing on developming personalized HIPEC treatment. This involves thorough investigations of different hyperthermia temperatures and durations, and various chemotherapeutic agents on multiple cell lines and mouse models.
4) Development of tests to predict normal tissue damage after radiotherapy and/or hyperthermia. Normal tissue damage after radiotherapy is a major problem in the clinic. Therefore in the lab special markers are investigated that can predict late normal tissue damage.