About 25% of primary human breast cancers are due to the deregulated expression of ErbB2/HER2. HER2- targeted therapies have improved patient survival, but both de novo and acquired resistance remain a challenge, as only 25% of treated patients respond to the current therapies. The inventors have identified that Moesin, a member of the ERM (Ezrin, Radixin and Moesin) protein family, is an allosteric inhibitor of HER2 activity. Moesin expression level is inversely correlated with HER2 expression level in human breast cancers. Besides, a low Moesin expression level is associated with a bad prognosis of HER2+ breast cancer patients. This allows further stratification of HER2+ breast cancer patients thereby offering novel personalized treatment options based on the administration of Moesin mimicking compounds (e.g. Zuclopenthixol derivatives) for HER2 inhibition.
Keywords: ERBB2, HER2+ breast cancers, Diagnostic/prognostic biomarkers, Moesin, Equivocal HER2 status