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Cytohesin inhibitors - An innovative approach for the inhibition of EGFR signalling

11.04.2013
Signalling of receptor tyrosine kinases such as EGFR is mediated by the extracellular binding of ligands triggering autophosphorylation. Until present this has been thought to be both necessary and sufficient for activating downstream signalling.

Surprisingly, cytoplasmic factors which regulate EGFR activation have been identified by the inventors. Inhibition of these so-called cytohesins decreased EGFR signalling whereas cytohesin overexpression stimulated receptor activation. With cytohesins thus being an interesting target for compounds treating cancer, the inventors have evaluated small molecules which exhibit a high selectivity for cytohesins as well as a low toxicity. They were able to demonstrate that the inhibition of cytohesins resulted in a reduced proliferation of EGFR-dependent lung cancer cells in vitro and in vivo. Furthermore, it was found that the substances exhibit a strong inhibition of glioblastoma cell proliferation. Additional data give reason to expect synergistic effects of a simultaneous treatment of cytohesin inhibitors and state of the art tyrosine kinase inhibitors.

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