Innovative Molecular Technology Simultaneously Silences 'Undruggable' Cancer Genes and Targets Tumors

Researchers at the University of North Carolina Lineberger Comprehensive Cancer Center have pioneered a groundbreaking molecular platform capable of tackling two of the most challenging cancer-related genes, KRAS and MYC, through a single 'two-in-one' molecule. This cutting-edge approach not only silences these notoriously difficult-to-target genes but also enables direct delivery of therapeutic agents to tumors expressing these genes, offering new hope for hard-to-treat cancers.

This novel technology employs specially designed inverted RNA interference (RNAi) molecules that can effectively co-silence mutated KRAS and overexpressed MYC genes. RNAi is a natural cellular process where small interfering RNAs (siRNAs) selectively deactivate specific mutated genes. The new molecules demonstrated a remarkable up to 40-fold increase in inhibiting cancer cell viability compared to traditional methods using individual siRNAs.

The significance of this innovation was published in the Journal of Clinical Investigation on July 31. Dr. Chad V. Pecot, the study’s lead author and professor at UNC School of Medicine, emphasized its potential: "Targeting both cancer-driving genes simultaneously is like attacking both Achilles heels of the disease, presenting tremendous therapeutic promise. Our dual-silencing molecule establishes proof-of-concept for this approach and could be adapted to target other gene pairs of interest."

Both KRAS and MYC play pivotal roles in promoting aggressive tumor growth by stimulating inflammation, activating survival pathways, and suppressing cell death mechanisms. Mutated KRAS is found in nearly 25% of all human cancers, especially prevalent in lung, colorectal, and pancreatic cancers, while MYC dysfunction occurs in 50-70% of cancers. Historically, MYC has been difficult to target with drugs, making this dual approach particularly impactful.

Dr. Pecot highlighted that their molecule offers a versatile platform, potentially enabling the silencing of three or more targets, which is especially valuable given that many cancers depend on multiple genetic mutations for survival.

This research builds on prior work where the team developed a targeted delivery system for a specific KRAS variant, KRAS G12V. The current broader approach could treat a larger patient population, including those with common KRAS mutations across several cancer types. According to the American Cancer Society, lung, colorectal, and pancreatic cancers accounting for nearly half a million new cases in the U.S. this year could benefit from such therapies.

Overall, this advancement exemplifies the promise of RNA-based therapeutics, bringing new avenues for effective treatment strategies against resistant cancers, and opens the door for further development targeting multiple genetic drivers in oncology.