“Two-in-One” Molecule Targets Two ‘Undruggable’ Cancer Genes, Showing Promise for Treating Aggressive Tumors

Researchers at the University of North Carolina Health Care and the University of North Carolina Lineberger Comprehensive Cancer Center have made a significant breakthrough in cancer treatment technology. They have developed a novel molecule that can simultaneously target and silence two notoriously difficult-to-target cancer-related genes, KRAS and MYC, which are responsible for promoting and maintaining aggressive tumor development.

The new technology incorporates a unique composition of inverted RNAi molecules that have shown a marked ability to co-silence mutated KRAS and over-expressed MYC. This advance holds special promise for treating cancers that have been historically challenging to treat, such as lung, colorectal, and pancreatic cancers, which account for nearly half a million new cases in the U.S. this year.

According to Dr. Chad V. Pecot, the corresponding author of the study and professor of medicine at UNC School of Medicine, targeting both cancer-causing genes at the same time is akin to slicing both Achilles heels of cancer. This technology has the potential to bring real hope to patients with KRAS-related cancers, which are often resistant to existing treatments.

The laboratory findings, published in the Journal of Clinical Investigation on July 31, showed that the co-silencing resulted in up to a 40-fold improvement in inhibition of cancer cell viability compared to the use of individual siRNAs. The researchers also made the first “two-in-one” molecule capable of silencing both the KRAS and MYC proteins, which are often deregulated in cancer cells.

KRAS mutations are present in nearly 25% of all human cancers, and MYC is considered a critical cancer-related gene, with dysfunction observed in approximately 50-70% of cancers. The co-silencing of these two genes has been shown to inhibit tumor development and promote cancer cell death.

“This is a game-changer for cancer treatment,” said Dr. Pecot. “Our technology has the potential to revolutionize the way we approach cancer therapy, and we are excited to explore its applications further.”

The researchers believe that this technology has broad implications, not just for targeting KRAS and MYC, but for any two genes of interest. They are now exploring the possibility of silencing three targets at once, which could further enhance the effectiveness of the treatment.

“This is another nice example of RNA therapeutics being made at UNC as part of the RNA Discovery Center,” Dr. Pecot said. “These advances could bring real hope to patients with KRAS-related cancers.”

The study’s findings have been published in the Journal of Clinical Investigation and are available online. The researchers are now planning to conduct further studies to explore the potential of this technology in treating various types of cancer.

Key Findings:

• The new molecule can simultaneously target and silence two notoriously difficult-to-target cancer-related genes, KRAS and MYC.
• The co-silencing resulted in up to a 40-fold improvement in inhibition of cancer cell viability compared to the use of individual siRNAs.
• The researchers made the first “two-in-one” molecule capable of silencing both the KRAS and MYC proteins.
• KRAS mutations are present in nearly 25% of all human cancers, and MYC is considered a critical cancer-related gene, with dysfunction observed in approximately 50-70% of cancers.
• The co-silencing of these two genes has been shown to inhibit tumor development and promote cancer cell death.