An experimental oral agent called 17-DMAG may help overcome this problem, according to a new study by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
Their laboratory and animal findings indicate that this agent is highly selective for chronic lymphocytic leukemia (CLL) cells and has minimal effect on normal immune cells, suggesting that it may leave a patient’s immune system healthy, the researchers say.
“This agent turns off multiple proteins that cancer cells need to survive, and we show that this activity occurs both in CLL cells from patients and in a CLL mouse model,” says study leader Amy J. Johnson, an assistant professor in the Division of Hematology and Oncology and a researcher with Ohio State’s Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute.
“Our findings strongly support testing this agent in CLL patients in a phase I clinical trial,” Johnson says.
The research will be presented at 5:45 p.m. CST Monday, December 7, 2009 during the 51st Annual Meeting of the American Society of Hematology in New Orleans.
The drug significantly prolonged survival in a CLL mouse model. Animals treated with the agent survived an average of 75 days, compared with 66 days for animals that didn’t receive it.
The agent works by inhibiting the action of a protein called HSP90, which is active mainly in CLL cells. This protein accompanies and protects – or chaperones – other proteins as they are being made by CLL cells.
These other proteins include AKT, RAF and Zap-70, all of which are important for the survival and growth of the cancer cells. Blocking the chaperone protein leads to the destruction of the other proteins.
In addition, the agent re-activates a gene called FOXD3, which, the same research group showed in earlier work, becomes silenced early during human CLL development, a change that is likely to play an important role in CLL progression.
Funding from National Cancer Institute, the CLL Research Consortium, The Leukemia & Lymphoma Society, and The D. Warren Brown Foundation supported this research.
Other Ohio State researchers involved in this study were Erin Hertlein, Thomas S. Lin, Amy J. Wagner, William H. Towns II, Virginia M. Goettl, Xiaoli Zhang, David Jarjoura, Chelsey A. Raymond, Derek A. West and John C. Byrd.
The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top 20 cancer hospitals in the nation, The James (www.jamesline.com) is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only five centers in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.
Medical Center Communications