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The article discusses the need for new therapeutic approaches for cancers that overexpress the Human epidermal growth factor receptor 2 (HER2) due to resistance mechanisms and toxicity associated with current therapies. The article highlights that HER2 is stabilized in a catalytically repressed state by a direct interaction with members of the ezrin/radixin/moesin (ERM) family. In HER2‐overexpressing tumors, the low expression of moesin contributes to aberrant activation of HER2. The article suggests that ebselen oxide, a compound identified through a screen designed to find moesin‐mimicking compounds, is an efficient allosteric inhibitor of HER2, which can selectively inhibit proliferation of HER2+ cancer cells and can show a significant benefit in combination with current anti-HER2 therapeutic agents. Finally, ebselen oxide significantly blocked HER2+ breast tumor progression in vivo. The article concludes that ebselen oxide is a newly identified allosteric inhibitor of HER2 that can be considered for therapeutic intervention on HER2+ cancers.
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