Targeting the oncogene and kinome chaperone CDC37

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Abstract
CDC37 is oncogenic because it stabilizes the structures of mutated or overexpressed oncogenic kinases. Targeting this chaperone activity, on which many tumours depend, is therefore an attractive option for broad-based therapy. CDC37 is a molecular chaperone that physically stabilizes the catalytic domains found in protein kinases and is therefore a wide-spectrum regulator of protein phosphorylation. It is also an overexpressed oncoprotein that mediates carcinogenesis by stabilizing the compromised structures of mutant and/or overexpressed oncogenic kinases. Recent work shows that such dependency of malignant cells on increased CDC37 expression is a vulnerability that can be targeted in cancer by agents that deplete or inhibit CDC37. CDC37 is thus a candidate for broad-spectrum molecular cancer therapy.