Overcoming Drug Resistant Prostate Cancer with APE1/Ref 1 Blockade
Technical Report,30 Sep 2014,29 Sep 2015
TRUSTEES OF INDIANA UNIVERSITY Indianapolis United States
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We have identified a new target that might explain how advanced prostate cancer cells avoid being killed by chemotherapy Apurinicapyrimidinic endonucleaseredox-factor 1, or simply, Ref-1, for short. In this report, we provide evidence that APE1Ref-1 is induced in prostate cancer cells and in human prostate cancer. This expression correlates to inflammation and to survivin signaling in human prostate cancer specimens. Genetic knockdown of APE1Ref-1 disrupts prostate cancer cell growth and survival in cell culture. In addition, inhibition of the redox function selectively of Ref-1 results in cell growth inhibition, with this therapy preferentially inhibiting prostate cancer cell growth above that in non-cancerous cells. Specific blockade of Ref-1 redox activity in tumors is a novel concept in tumor therapy. If we are successful, we will have defined a critical therapeutic target for drug-resistant prostate cancers, and logically clinical trials would follow targeting this pathway.