Targeting components of the Wnt signaling pathway in gastrointestinal tumors

In colorectal cancer deregulation of the Wnt pathway is a major cause for malignancy. Within this project potential therapeutic targets are identified and selective knockdown on the mRNA level carried out with the RNAi technology. For this purpose, receptor targeted carriers for siRNA are applied first ex vivo and thereafter in relevant tumor models in vivo. The influence of target knockdown on tumor cells in terms of invasiveness, colony formation and proliferation are studied in vitro. After systemic application of targeted siRNA carries, specific knockdown is analyzed by QPCR and therapeutic efficacy in a disseminated liver metastasis model of human colorectal cancer shown by bioluminescence imaging of gene marked tumor cells and histological analyses.

Reference

  • Cengizeroglu, A, Farkasova, K, Deutsch, D, Haase, R, Anton, M, Wagner, E, Ogris, M. (2010) Harnessing Molecular Targets in Human Colon Cancer Cells for Tumor Specific RNAi and pDNA-Based Therapies. 7th Annual Meeting of German-Society-for-Gene-Therapy (DG-GT e.V.) OCT 07-09, 2010 LMU Campus Grosshadern, Munich, GERMANY Human Gene Therapy 21: 1205-1205.  (printout available on request)