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Scientists Silence Leading Cancer-Causing Gene

Nov 15, 2014 12:55 PM EST

In new breakthrough research, scientists have successfully silenced a leading cancer-causing gene, an elusive protein called KRAS, which can hopefully one day lead to the development of more effective target drug therapies.

More specifically, KRAS is a signaling molecule that when mutated, triggers a series of events which result in constant cell division, allowing cancer cells to grow and survive. KRAS mutations are present in roughly 30 percent of human cancers, particularly lung, colon, pancreatic, and thyroid.

"KRAS was one of the first cancer-causing genes ever discovered, and it was the obvious target to go after. People have been trying for decades to hit it, but they haven't had much luck," lead author Chad Pecot, with the University of North Carolina School of Medicine, said in a statement.

That is, until now. Pecot and his colleagues, along with researchers at the University of Texas MD Anderson Cancer Center, developed a new approach to block the KRAS oncogene. They relied on bits of synthetically engineered RNA, which not only dramatically stunted the growth of lung and colon cancers in cultured cells and mice, but also stopped cancer cells from spreading to other parts of the body - the main cause of fatalities.

Binding drugs to KRAS is notoriously difficult due to its lack of good pockets or crevices, and targeting the proteins downstream in the KRAS signaling cascade has also been wildly unsuccessful in the past. So instead, Pecot turned to a new genetic tool known as RNA interference - or RNAi - to destroy the KRAS protein before it even fully forms.

There are several types of RNA - the single-stranded molecule transcribed from DNA - and one of them is known as mRNA, responsible for sending genetic messages. In this study, researchers created similar type of small interfering RNA, or siRNA, that was programmed to recognize messages from KRAS as enemies. By doing so, siRNAs destroyed more than 90 percent of the KRAS gene messages, significantly impairing the growth of cancer cells.

Not only did siRNA halt cell division, but in addition it reduced the number of secondary tumor growths by 80 percent in mice with lung cancer, as well as made colon cancer tumors 69 percent smaller.

The findings, published in the journal Molecular Cancer Therapeutics, are promising for future drug therapies, as it shows "that KRAS is druggable if you use outside-the-box methods," Pecot concluded.

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