Complete researchers from the University of North Lineberger have developed a “two in one” molecule which can simultaneously deactivate two genes notoriously difficult to target cancer, Kras et Mycas well as directly deliver drugs to tumors that express these genes. This advance is a particular promise for the treatment of cancers that have been historically difficult to treat.
The new technology incorporates new compositions of inverted Arni molecules which have shown a marked capacity to co-sit Kras and overexpressed Myc. RNA interference (ARNI) is a cellular process that uses small interferenced RNAs (SIRNA) to deactivate selectively or silence, mutated genes. Co-silencious has resulted in an improvement up to 40 times of the inhibition of the viability of cancer cells compared to the use of individual SIRNA.
Laboratory results were published in the Journal of Clinical Investigation July 31.
“The targeting of two carcinogenic genes at the same time is related to slicing the two Achilles of cancer heels, which has enormous potential,” said Chad V. Pecot, MD, corresponding author of the article, professor of medicine at UNC School of Medicine. “Our inverted molecule establishes proof of concept Kras et Myc In cancer and constitutes an innovative molecular strategy for the co-target not only these two genes, but two genes of interest, which have great implications. “”
Transferred Kras et Myc Can work together to promote and maintain aggressive tumor development through several mechanisms, including stimulation of inflammation, activation of the survival routes of cancer cells and the suppression of the death of cancer cells.
Kras Mutations are present in almost 25% of all human cancers, and they occur frequently in some of the most common types of tumors. Myc is also considered a critical gene linked to cancer and is dysfunctional in around 50 to 70% of cancers. Several studies have shown that the inactivation of Myc Can inhibit tumor development considerably, making it a very attractive therapeutic co-target.
« Myc seems to be an almost important target as KrasHowever, there are still no successful drugs capable of targeting Myc“Said Pecot, a co-leader of the UNC Lineberger Cancer therapeutic program and director of the UNC RNA discovery center. Our study is one of the first to deeply characterize the therapeutic implications to target the two genes at the same time. We also made the first “two in one” molecule capable of silencing Kras and Myc proteins “.
Since most cancers depend on several genetic mutations, or engines, for survival, this technology is particularly precious to target two key motors at the same time. He keeps a particular promise when the two targets, as Myc et Krasare essential to the ability of the cancer cell to stay alive, but have historically been difficult to deal with with drugs. Peccot noted that the unique characteristics of their design allow you to start exploring the ability to silence three targets at a time. “The opportunities are large,” he says.
This discovery is based on a related discovery of the Pecot laboratory published in Cancer cell in June, which described a targeted drug administration mechanism for a Kras variant known as the name KRAS G12V. Now Pecot and his colleagues have developed a RNA sileting molecule capable of closing everything Kras Mutations found in cancer.
While this broader approach is less specific than the previous one KRAS G12V– Targeted method, it has the potential to treat a much larger group of patients, including those with the most common KRAS mutations found in pulmonary, colorectal and pancreatic cancers. Together, these cancers are expected to represent nearly half a million new cases in the United States this year, according to American Cancer Society.
“Overall, this is another fine example of RNA therapy made at UNC as part of the RNA discovery center,” said Pecot. “These advances could bring real hope to patients with Kras– Linked cancers. “”