PhD ceremony Ms. M. Sie: Angiogenesis in pediatric brain tumors: therapeutic possibilities?

PhD ceremony: Ms. M. Sie, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Angiogenesis in pediatric brain tumors: therapeutic possibilities?

Promotor(s): prof. E.S.J.M. de Bont, prof. W.A. Kamps

Faculty: Medical Sciences

Brain tumors are the most frequent pediatric tumors and are still the leading cause of cancer morbidity and mortality among children, despite different therapeutic modalities including neurosurgery, chemotherapy and radiation. Moreover, morbidity can be serious, mainly because of the localization of the tumor and its subsequent chance of surgical morbidity and dismal effect of chemotherapy and/or radiation. So to reduce this morbidity as well as mortality, stimulating healthy ageing, new therapeutic modalities are needed.

As angiogenesis, the formation of vessels from a pre-existing vasculature, is highly crucial in tumor growth and progression, this mechanism has been extensively investigated and different anti-angiogenic therapies have been developed. However these studies are limited in pediatric brain tumors. So the present thesis obtained to increase insight into the angiogenic profile, tumor vasculature and growth-factor-driven resistance to angiogenic inhibitors in pediatric brain tumors including low grade astrocytoma and ependymoma. This thesis suggested a therapeutic window for anti-angiogenic therapy in these tumors at the one site and at the other site highlighted the possible tumor escape mechanisms that can arise in response to anti-angiogenic therapy. To further increase insight into these mechanisms and to test potential angiogenic agents, preclinical analyses need to be optimized, making translation into clinical trials more rational. Eventually, more individualized anti-angiogenic therapy will be a worthwhile future perspective in pediatric brain tumors.