A paper published today by Science Translational Medicine outlines the process by which a category of anticancer drugs called curaxins inhibit tumor cell growth and division. Roswell Park Cancer Institute (RPCI) researcher Katerina Gurova, MD, PhD, was principal investigator for the study, which represents the first published research on this class of agents, working in collaboration with a team that included several investigators from Cleveland BioLabs, Inc. (CBLI).
In the paper, "Curaxins: Anticancer Compounds that Simultaneously Suppress NF-kB and Activate p53 by Targeting FACT," Dr. Gurova and her colleagues characterize for the first time the mechanism by which curaxins activate p53 and inhibit NFkappaB, pathways that are frequently deregulated in cancer cells. The operation of curaxins, they found, is mediated by functional inactivation of a chromatin-remodeling complex called FACT (facilitates chromatin transcription).
"By hitting multiple cancer treatment targets, curaxins resemble long-known and very efficacious anticancer drugs such as doxorubicin or cisplatin, but without their genotoxicity, which is the main challenge of historical chemotherapies," said co-author Andrei V. Gudkov, PhD, DSci, Senior Vice President of Basic Science and The Garman Family Chair in Cell Stress Biology at RPCI, and Chief Scientific Officer of both CBLI and Incuron LLC, a Moscow-based CBLI affiliate that develops curaxins. "Our studies continue to reinforce our belief that curaxins are promising drug candidates that may be effective against a wide range of cancer types."
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