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Báo cáo khoa học: M1 – Peptidomimetics and Signal Transduction Inhibition

Cancer cells develop strong anti-apoptotic signaling pathways and therefore escape many therapeutic regimens. Recognizing this feature of cancer cells, we have focused on two approaches: dis-arming the cancer cell from its anti-apoptotic weaponry [1, 2] and applying strategies aimed at enhancing pro-apoptotic signa-ling pathways selectively in the cancer cell [3]. The first goal has been achieved by developing highly selective Aktstatins [1, 2] that inhibit PKB 100 times better than PKA or PKC. | Abstracts M1 - Peptidomimetics and Signal Transduction Inhibition M1-001 Tricking cancer cells to die A. Levitzki Unit of Cellular Signaling Department of Biological Chemistry The Alexander Silberman Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem Israel. E-mail levitzki@vms.huji.ac.il Cancer cells develop strong anti-apoptotic signaling pathways and therefore escape many therapeutic regimens. Recognizing this feature of cancer cells we have focused on two approaches disarming the cancer cell from its anti-apoptotic weaponry 1 2 and applying strategies aimed at enhancing pro-apoptotic signaling pathways selectively in the cancer cell 3 . The first goal has been achieved by developing highly selective Aktstatins 1 2 that inhibit PKB 100 times better than PKA or PKC. These inhibitors are highly non-toxic inhibit Akt PKB induced phosphorylation in cells and in vivo and are highly effective as anti-tumor agents in vivo. The complementary strategy is to enhance pro-apoptotic 520 Abstracts signaling pathways selectively in cancer cells 3 . One of the key elements is to induce in the targeted cancer cells signaling pathways that induce strong by-stander effects killing pretty fast not only the targeted cells but also the neighboring cancer cells that do not express the target a common situation in the heterogeneous human tumor. We have achieved this goal for tumors overexpressing the EGF receptors by targeting them with EGF guided non-viral vectors loaded with double stranded RNA. These dsRNA molecules are internalized by EGF receptor mediated endocytosis and kill only cells that over-express wild type EGFR and neighboring tumor cells co-growing with the targeted cells. Using this targeted polyIC we are able to cure mice bearing sizable intracranial human Glioblastma Multiforme GBM without harming normal brain tissue 4 . References 1. Reuveni H Livnah N Geiger T Klein S Ohne O Cohen I Benhar M Gellerman G Levitzki A. Toward a PKB inhibitor .