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Cancer drug cisplatin found to bind like glue in cellular RNA
Date:11/21/2011

oncentration on RNA. Moreover, the drug bound like glue to specific sections of RNA.

DeRose is now pursuing the ramifications of the findings. "Can this drug be made to be more or less reactive to specific RNAs?" she said. "Might we be able to go after these new targets and thereby reduce the drug's toxicity?"

While cisplatin is effective in reducing tumor size, its use often is halted because of toxicity issues, including renal insufficiency, tinnitus, anemia, gastrointestinal problems and nerve damage.

The extensive roles of RNA have come under intense scrutiny since completion of the human genome opened new windows on DNA, life's building blocks. It had been assumed that RNA was simply a messenger that coded for protein activity. New technologies, DeRose said, have shown that a vast amount of RNA performs an amazing level of different functions in gene expression, controlling it in specific ways during development or disease, particularly in cancer cells.

In this project, DeRose's team only explored cisplatin's binding on two forms of RNA: ribosomes, where the highest concentration of the drug was found; and messenger RNA. There are more areas to be looked at, said DeRose, whose group initially developed experience using and mapping platinum's activity as a mimic for other metals in her research on RNA enzymes.

DeRose is now planning work with UO colleague Hui Zong, a biologist studying how cancer emerges, to extend the research into mouse cells to see if the findings in yeast RNA hold up. An additional collaboration with UO chemist Michael Haley involves the creation of new platinum-based drugs with "reaction handles" that will allow researchers to easily pull the experimental drugs out of cells, while still attached to their biological targets. New developments in 'deep' RNA sequencing, available through the UO's Genomic Core Facilities, could then provide a much broader view of platinum's preferred resting sites in
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Contact: Jim Barlow
jebarlow@uoregon.edu
541-346-3481
University of Oregon
Source:Eurekalert  

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