| The research theme concerning treatment of cancer is intense in all three participating institutes. It can be divided in the following research areas: chemotherapy, immunotherapy, radiotherapy and gene therapy, or a combination of these modalities. Thus, high dose chemotherapy in combination with autologous or allogenic stem cell transplantation is an important subject. Within the area of chemotherapy emphasis lies on pharmacokinetics and pharmacodynamics, either or not in relation to (multi)drug resistance. Resistance is a crucial determinant of chemotherapy; the value of classical resistance parameters is assessed in clinical studies, while new resistance targets are studied in in vitro systems and experimental animal models. Recognition of individual variations in drug sensitivity and resistance should lead to a more individualized treatment of cancer. Once improved treatment modalities are designed, the coordination of multi-center trials is crucial. Indeed, development and testing of new anticancer agents remains a major task of the EORTC, which coordinates trials throughout Europe. Similarly, the EORTC plays a role in patient trials on chemoprevention. Insight into the mechanism by which factors produced by tumor cells influence angiogenesis will lead to improved treatment of cancer, either or not in combination with chemotherapeutic treatment. Immunotherapy is a treatment modality that is still rapidly developing. New approaches of immunotherapy are developed on basis of fundamental research, tested in animal models and being implemented in clinical trials. Different approaches involve boosting of the endogenous immune response, but also active immunisation by vaccination with dendritic tumor cells and passive immunisation with tumor specific lymphocytes that have been expanded in vitro. Research into radiotherapy aims at optimising treatment protocols as well as the clinical implementation of new modalities such as boron neutron capture therapy for brain tumors and photodynamic therapy for gastrointestinal tumors. In Gene therapy the most important aims are a. specific and efficient targeting of viral vectors to tumor cells, using the proper surface determinants; b. development of improved viral vectors in which efficient cytotoxic genes are driven by tumorspecific promoters. The cytotoxic genes may either code for enzymes that convert prodrugs, or encode genes that induce apoptosis in the target cells. One of the approaches is the use of conditionally replicating viruses (CRADS) that have considerably higher efficiency in cell killing due to replication within the target cell. Finally, trials are performed to improve protocols for surgery of tumors with special attention to the combination of chemotherapy and surgery. |
