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Abstract
Grant Number: 1R03MH076408-01 Project Title: Isolation of Inhibitors of Her-Kinase Expression (RMI)
PI Information: Name Title CHIOSIS, GABRIELA chiosisg@mskcc.org Abstract: DESCRIPTION (provided by applicant): Human, cancers frequently express high levels of transmembrane tyrosine kinases of the Her family. Overexpression of at least one of these, the Her2 receptor, has been associated with a more aggressive behavior. Several therapeutic strategies targeting the receptor are now in various stages of clinical development. Most of the known agents block the activation or inhibit the activity of Her2; however, a more significant therapeutic outcome may result from degrading this oncoprotein. We propose here a cell-based assay that may be used to conduct high-throughput screens (HTS) to isolate Her2 kinase expression inhibitors. The compounds identified from these efforts will represent important leads that will serve as the starting point to obtain drugs that modulate Her2 expression. These drugs could, in principle, be used to treat patients with advanced cancers driven by Her2-overexpression/oversignalling. Given the importance of Her-kinases in human disease, the time is ripe to design and perform a large-scale screening regimen to identify Her-kinase expression modulators. To our knowledge, this has not been accomplished, and we believe that we are uniquely positioned to initiate this goal.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
aggression, antineoplastic, drug discovery /isolation, drug screening /evaluation, enzyme induction /repression, neoplasm /cancer, oncoprotein, protein tyrosine kinase, receptor expression
bioassay, enzyme activity, high throughput technology, method development, protein degradation
tissue /cell culture
Institution: SLOAN-KETTERING INSTITUTE FOR CANCER RES 1275 YORK AVE NEW YORK, NY 10065 Fiscal Year: 2005 Department: Project Start: 15-SEP-2005 Project End: 30-SEP-2007 ICD: NATIONAL INSTITUTE OF MENTAL HEALTH IRG: ZMH1