January 25, 2016
There is a brand new way to target cancers, and cancer biologist Marikki Laiho, M.D., Ph.D., the Willard and Lillian Hackerman Professor in Radiation Oncology, is one of only two scientists in the country funded by the National Institutes of Health to work on it. It's called RNA polymerase I transcription.
This adventure in new science began when Laiho's group discovered a small synthetic chemical molecule, called BMH-21, and showed that it has a unique way of killing cancer cells. "We learned that the molecule is a novel inhibitor of RNA polymerase I," she says. "RNA polymerase I transcription is an intricately coordinated transcriptional program. It is highly activated and insufficiently controlled in cancers, but despite its ability to support cancer growth, it has received little attention as a possible new target for therapy."
Transcription in this case means "reading the DNA into RNA, that is, converting the universal genetic code into a new biomolecule, RNA," says Laiho. "RNA polymerase I drives a fundamental process that synthesizes the RNA component for the ribosomes (tiny factories inside cells where proteins are made), and hence, is essential for making cellular proteins. These building blocks are necessary for the life and health of cells. For this reason, this pathway has been considered untouchable, and efforts have not been invested to exploit it as an avenue to deactivate cancer cells. But our research has proven otherwise."
Laiho's findings suggest the promise of inhibiting RNA polymerase I transcription in a potential new class of cancer-fighting drugs. "We have shown that it has therapeutic benefit, and it is well-tolerated in preclinical models. We hope that our findings will invigorate basic science efforts on RNA polymerase I transcription. We still lack basic knowledge of the factors associated with this fundamental process and their regulation."
Laiho believes BMH-21 has "particular relevance for the treatment of prostate cancers," and is turning her work toward developing this molecule into a clinical drug. Her team has received the Harrington Discovery Institute's Harrington-Scholar Innovator Award and the Prostate Cancer Foundation Global Challenge Award for this work. Laiho and colleagues are now exploring the role of BMH-21 in advanced prostate cancer.