Scientists at the University of North Carolina Lineberger Comprehensive Cancer Center have engineered a “two-in-one” molecule capable of simultaneously silencing two notoriously hard-to-target cancer-related genes—KRAS and MYC—while directly delivering drugs to tumors that express these genes. This innovation offers new hope for treating cancers that have long resisted effective therapies.
Novel RNAi-Based Approach
As reported by medicalxpress, the new technology uses advanced compositions of inverted RNA interference (RNAi) molecules designed to co-silence mutated KRAS and over-expressed MYC. RNAi harnesses small interfering RNAs (siRNAs) to selectively switch off mutated genes. In laboratory studies, co-silencing both genes improved inhibition of cancer cell viability by up to 40-fold compared to using individual siRNAs alone. These findings were published in the Journal of Clinical Investigation on July 31.
Dual Targeting: “Slicing Both Achilles Heels”
“Targeting two cancer-causing genes at the same time is akin to slicing both Achilles heels of cancer, which has tremendous potential,” said Chad V. Pecot, MD, corresponding author, professor of medicine at UNC School of Medicine, co-leader of the UNC Cancer Therapeutics Program, and director of the UNC RNA Discovery Center. “Our inverted molecule establishes proof-of-concept for dual-silencing KRAS and MYC and offers a platform to co-target any two genes of interest.”
Why KRAS and MYC Are Key Targets
Nearly 25% of all human cancers, especially lung, colorectal, and pancreatic tumors, have KRAS mutations. About 50–70% of cancers show dysfunctional MYC, which drives aggressive tumor growth. Although several studies demonstrate that inactivating MYC can drastically inhibit tumor development, no effective drugs currently target it. Mutated KRAS and MYC often work together to promote cancer by stimulating inflammation, activating survival pathways, and suppressing cancer cell death.
Potential to Expand Beyond Two Targets
Because most cancers rely on multiple genetic “drivers” for survival, this dual-targeting technology holds particular value when both targets are critical for tumor growth. Pecot emphasized that their unique molecular design could even make it possible to silence three genes at once. “The opportunities are vast,” he noted.
Building on Previous Success
This discovery builds on Pecot’s earlier work, published in Cancer Cell in June, which described a targeted drug delivery method for the KRAS G12V variant. Now, his team has developed an RNA silencing molecule that can shut down all KRAS mutations found in cancer. While this broader approach is less specific than the KRAS G12V-focused strategy, it has the potential to benefit a much larger patient population—particularly those with lung, colorectal, and pancreatic cancers, which together could account for nearly half a million new U.S. cases this year.
Hope for KRAS-Related Cancers
Pecot highlighted the broader impact of this advancement: “This is another strong example of RNA therapeutics being developed at UNC. These advances could bring real hope to patients with KRAS-related cancers.”