Molecular Cancer Biology Program
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About the research
In addition to oncogenic mutations that act cell-autonomously, tumor cell growth depends on interactions with its microenvironment. Tumor microenvironment consists of cells of hematopoietic and mesenchymal origin, including inflammatory cells, stem and progenitor cells, fibroblasts, endothelial cells and vascular mural cells. Tumor cell growth is known to depend on the interaction of tumor cells with such stromal cells. For example, growing tumor needs to recruit normal endothelial and vascular mural cells to form its blood vessels. In addition, tumor cells induce stromal cells to secrete factors that contribute to tumor cell growth and invasion. Stromal cell -dependent interactions represent an attractive target for cancer therapy, because normal cells are genetically stable, and would not be expected to develop resistance to therapeutic agents. The development of such therapies is hampered by the fact that the molecular mechanisms behind tumor-stroma interactions are often poorly understood.
The "TUMOR-HOST GENOMICS" project links together the resources of five European leading-edge laboratories studying major signaling pathways in mesenchymal and hematopoietic cells, forming a concerted effort to understand tumor-host interactions, and to identify novel therapeutic targets. The workplan entails development of novel advanced functional genomics instruments, technologies and methods to study tumor-host interactions in cancer, and to apply these techniques to the identification of molecules and processes in normal cells which could be targeted by novel anti-cancer therapeutic agents. In addition, we will develop targeted lentiviruses which would allow in vivo delivery of therapeutic agents into tumors. Functional validation of the discovered targets and developed delivery systems will be performed in vivo models of murine tumor growth and dissemination. The work has significant exploitation potential and applications for health in the understanding of the molecular mechanisms of tumor-host interactions, and in the treatment of cancer.
Fig. 1 . Summary of the science and technology objectives of the project, and the work package structure. The project aims to develop novel tools and methods to study tumor-host interactions in cancer, and to apply these techniques to the identification of molecules and processes in normal cells which could be targeted by novel anti-cancer therapeutic agents. In addition, we also propose to develop targeted lentiviruses that specifically express genes in bone marrow-derived cells and/or in endothelial cells, which would allow in vivo delivery of therapeutic agents into tumors. Abbreviations: BM, bone marrow; RNAi, RNA interference; WP, work package.
Page updated December 22, 2009