In Two Drug Screens, New Technique Identified Compounds That Turned Off the Myeloma Survival Factor IRF4 or Turned On the Tumor Suppressor CDKN2A
September 13, 2012
Researchers at Cleveland Clinic’s Taussig Cancer Institute have developed a drug screening method that dramatically simplifies the analysis of gene activity, according to research published today in PLOS ONE.
While conventional techniques to analyze gene activity require extraction of the genomic material from cells and multiple experimental steps, this new method uses unprocessed cells and yields answers in three hours about the activity of an investigated gene with one experimental step. The new technique can be applied to screening thousands of small molecules for their ability to regulate the activity of genes important for cancer cells.
Investigators showed that this drug screening approach can identify novel molecules that reactivate a tumor suppressor gene – CDKN2A – which a variety cancer cells shut down. When active, it suppresses growth and enables aging and death of cancer cells.
This approach also identified small molecules that suppress interferon regulatory factor 4 (IRF4), a protein necessary for myeloma cell survival.
“The search for gene-targeted anti-myeloma drugs drove the development of this technique. It is very exciting to see that it already yielded three drug candidates that suppress production of IRF4 much more profoundly than any known drug,” said Frederic Reu, MD, associate staff physician in the department of Translational Hematology & Oncology Research at Taussig Cancer Institute “While our laboratory focuses on multiple myeloma, this method exploits fundamental principles of gene activity control and should be applicable to any gene of interest.”
Multiple myeloma is the second most common blood cancer. Although treatment options have improved in the last decade, cure is exceedingly rare.
The work was supported by a grant from the Scott Hamilton CARES Initiative and generous gifts from the R.T. Foundation on behalf of Robert J. Tomsich and Suzanne M. Tomsich, and from Nancy Vacc.
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