Glioblastomas: are individual therapies required for individual tumors?

Abstract

In contrast to most other malignant diseases, especially in children, up to now glioblastoma multiforma is a lethal diagnosis for most patients. Operation and radiotherapy are very effective to reduce the tumor burden, however, a strong adjuvant treatment is lacking. Due to rapid infiltrative growth, relapse is common, which can then no more be controlled in most of the cases. Many data are available on the cellular signaling and regulation networks in glioblastomas, particularly in the different growth factor receptor dependent pathways upregulated in these tumors. Numerous substances acting in a molecular way to inhibit these are at hand, but still, although these compounds showed some activity in individual patients, larger studies aiming at an improvement of the cure rate were generally disappointing. One reason for this might be the heterogeneity of tumors. Novel methods of molecular analysis showed that they are extremely heterogeneous - regarding genetic, epigenetic or signaling regulation, receptor expression, or interaction with stroma, vasculature, or the immune system. Another striking fact is that in glioblastomas of children and adolescents, completely different patterns of molecular setup are found compared to those in adults. Thus, probably a different therapeutical approach would be required for each tumor, using an individually selected panel of treatment modalities. For such an approach, besides many laboratory hurdles, also the concept of evidence based medicine has to be developed further to handle individualized medicine.