The new molecular technology targets tumors and simultaneously arbitrates two cancer genes “not prejudice”

Complete researchers from the Cancer Center of the University of North Carolina have developed a “two in one” molecule “which can simultaneously deactivate two genes notoriously difficult to target cancer, Kras and Myc, as 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 the mutated kras and to overexpressy 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 deciding 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 for the double silence of Kras and Myc in cancer and constitutes an innovative molecular strategy for co-targeting not only these two genes, but two genes of interest, which have general implications.”

Kras and MYC mutated 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 abolition of the death of cancer cells.

Kras mutations are present in almost 25% of all human cancers, and they often occur 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 considerably inhibit tumor development, making it a very attractive therapeutic co-target.

“Myc seems to be an almost as important target as Kras, but there are still no successful drugs capable of targeting myc,” said Pecot, co-leader of the therapeutic program Cancer of the UNC Lineberger and director of the Discovery Center of the UNC RNA. “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 molecule” two in a “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. It keeps a particular promise when the two targets, like MyC and Kras, are essential to the capacity 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 said.

This discovery is based on a related discovery of the Pecot laboratory published in Cancer cell In June, which described a targeted medication administration mechanism for a specific Kras variant known as Kras G12V. Now Peccot and his colleagues have developed a RNA silening molecule capable of closing all Kras mutations found in cancer.

Although this wider approach is less specific than the previous method targeted by Kras G12V, 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 cancer linked to Kras.”