Redirection of oncoproteins to kill cancer cells

Abstract

Oncogenic activity is often associated with altered intracellular protein localization and with specific gains of function, e.g., kinase activity. We propose, that intracellular redirection of oncogenic proteins towards novel targets can be used to specifically kill tumor cells. For example, an oncogenic kinase could be redirected to activate an apoptosis inducing protein. This redirection approach offers the advantages of high specificity (the oncogene is restricted to tumor cells) and potentially high activity since it makes use of the intrinsic functions of the oncogene. Also, the oncogene is not only functionally inhibited but it is turned against the cancer cell. Activity and specificity of the redirection therapy approach were demonstrated in AML1-ETO positive leukemia cells. A recombinant protein redirected the transcriptionally inhibitory AML1-ETO protein to essential proliferation-associated promoters. As a result, leukemia cells were inhibited with high effectivity and specificity. This approach can be utilized to target a wide variety of human cancers.