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KREFTSATS-Særutlysning kreftmidler, historikk

Critical regulatory networks for tumor-vascular interactions and activated angiogenesis in urogenital cancers

Tildelt: kr 6,6 mill.

Angiogenesis and tumor-vascular interactions are essential for tumor spread. We focus on this aspect since anti-angiogenic therapy avoid treatment resistance. Adhesion molecules are important for the ability of tumor cells to invade surrounding tumor stro ma and to enter the vascular systems (blood vessels, lymphatics), a prerequisite for distant metastatic spread and reduced survival. We have shown that deregulated expression of selected surface molecules (cadherins and catenins) are significant for clini cal progress of endometrial carcinomas, and angiogenesis is important for metastases in tumors (endometrial,prostate, breast, melanoma). Today there is a gap in our understanding of these processes, and how to predict treatment response. The goal of this project is to further explore the molecular determinants of tumor vascular interaction and vascular spread, by integrated DNA microarray (DMA), tissue microarray (TMA) and clinical validation studies. Microarray methods ensure the simultaneous examin ation of multiple markers and regulatory networks associated with predefined molecular pathways, such as cadherin-families, catenins, and the wnt-system. These studies are supported by advanced bioinformatics (CBU, FUGE platform). Invasion of tumor cells into vascular units, which has been documented in our previous studies, will be focused. Its detailed regulation remains to be established. Co-existence of reduced cell-cell adhesion (dysregulated surface molecules) and vascular invasion is of special int erest. Further, the relationship between tumor angiogenesis (microvessel density), vascular proliferation, vascular maturation and vascular invasion by tumor cells, will be studied, and we have preliminary data on the relative importance of these characte ristics. APPLICATION: This application focus on the regulation of tumor-vascular interaction and activated angiogenesis and the ability of related markers to predict therapy response and patient prognosis.


KREFTSATS-Særutlysning kreftmidler, historikk