Specific inhibition of heat-shock-protein 90 (Hsp90) by a novel peptidomimetic inhibitor shepherdin in malignant glioma cells

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Malignant gliomas are the most common type of brain tumors. The most common and malignant form of gliomas is known as glioblastoma multiforme (GBM), which accounts for approximately 60%–70% of the cases. Current standard-of-care therapy for GBM confers a median survival period of only 14.6 months. Heat-shock-protein 90 (Hsp90) is an attractive therapeutic target since it can bind a number of well-characterized client proteins, including many oncogenic signaling proteins being essential for progression and therapeutic resistance of GBM such as ErbB2, EGFR, Raf, MEK, PDGFR, Cdk-4, - 6, and -9, Akt, mutated p53 and survivin. Many of these proteins are the ones that are mutated or overexpressed in GBM. A novel specific inhibitor of Hsp90 is the peptidomimetic Shepherdin that has been shown to specifically target tumour cells whereas it has no effect on non-neoplastic cells. In this study Shepherdin will be evaluated as a potential new drug in treating GBM.