Researchers from Roswell Park, Cleveland BioLabs Publish Curaxins Findings

Paper in Science Translational Medicine is first publication on these anticancer agents and how they work.

BUFFALO, NY - 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 Comprehensive Cancer Center(Roswell Park) 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 Roswell Park, 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.”

As part of the team’s investigations, research into curaxins’ mechanism of action, as well as all preclinical testing of new compounds, was done at Roswell Park. From 2003-2007, Dr. Gurova led the team that discovered this class of agents.

A multicenter phase I single-dose ascending trial of CBLC102 (the predecessor of these curaxins, also known as quinacrine), is ongoing in patients with gastrointestinal and liver tumors in The Russian Federation (RF). A phase I clinical trial of the oral formulation of next-generation Curaxin CBLC137 in solid tumors is planned to start in the first quarter of 2012 in the RF, and an intravenous formulation of the compound is currently being developed to further optimize the bioavailability of CBLC137, with plans to initiate a phase I trial in the United States once preclinical preparations are completed.

Lead authors on the publication are Alexander V. Gasparianand Catherine A. Burkhart, both of CBLI. The paper is available at Science Translational Medicine’s website, http://stm.sciencemag.org.

The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Roswell Park, founded in 1898, was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit Roswell Park’s website at http://www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org.