Kärlen som mål för cancerterapi i hjärntumörer
Tidsperiod: 2017-01-01 till 2020-12-31
Projektledare: Anna Dimberg
Budget: 4 000 000 SEK
Glioblastomas are highly aggressive brain tumors, characterized by microvascular proliferation and dysfunctional vessels. The abnormal vessels contribute substantially to patient mortality. Still, the mechanisms underlying the abnormal vascular function and its role in tumor progression and resistance to therapyhas not yet been clarified.We have previously identified 95 differentially expressed genes, including CD93 and ELTD1, and pro-angiogenic growth factors, including pleiotrophin, associated with vascular abnormalization in glioblastoma. In this proposal, we analyze how these genes and growth factors affect vascular function and tumor development. The aim is to determine if proteins associated with vascular abnormalization can serve as therapeutic targets, and to find new treatment regimes for glioblastoma by usingvascular targeting strategies to improvecancer immunotherapy.The function of selected genes and growth factors will be analyzed using in vitro and in vivo models of angiogenesis, inflammation and glioma development and gene-targeted mice. Tumor tissue microarrays will be used to determine if protein expression correlates to patient survival. Vascular normalization strategies found to increase T-cell recruitment to the tumor, will be tested in combination with immunotherapy in clinically relevant experimental models of glioma.Our goal is to use vascular targetingto find new treatment regimes for glioma andimprove patient prognosis.