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The North Carolina Biotechnology Center awarded $100,000 to UNC Lineberger Comprehensive Cancer Center’s Chad Pecot, MD, to study an experimental treatment that would silence a gene commonly mutated in cancer.

UNC Lineberger's Chad Pecot, MD.
UNC Lineberger’s Chad Pecot, MD.

Using a Nobel Prize-winning technology called RNA interference or RNAi, Pecot’s lab designed an investigational drug to shut down the mutated version of the KRAS gene. The KRAS gene is frequently associated with many cancers – most notably lung, pancreatic and colon cancers. This gene is part of the RAS family of genes that are mutated in nearly a third of all cancers.

“It has huge implications in cancer,” said Pecot, who is an associate professor in the UNC School of Medicine Division of Hematology and Oncology. “KRAS is mutated in a tremendous amount of cancers.”

Pecot’s lab used RNAi technology to design an experimental therapy to silence the mutated KRAS gene. Andrew Z. Fire and Craig C. Mello won the Nobel Prize in 2006 for the discovery of “RNAi,” a mechanism for controlling the function of genes using RNA.

They found they could create segments of RNA, the language of proteins, to bind to genes of their choice, leading to their degradation.

Pecot identified segments of RNA that could bind and shut down any plans to turn mutated KRAS into proteins before those proteins are produced. They have evidence they can spare silencing of non-mutated KRAS genes in cells to prevent toxicity.

They are also studying how to optimize their experimental treatment, which is called EFTX-001, for delivery inside the body to tumors, and to prevent degradation of the treatment.

Opportunities in cancer research

While KRAS mutations were discovered in cancer decades ago, therapies that can shut down this mutation directly remained out of reach for years. Now, new developments have emerged, with clinical trials launched to test a compound that can target one particular type of KRAS mutation called KRAS G12C.

“A small molecule drug that inhibits the function of mutated KRAS has been really elusive,” Pecot said. “The G12C inhibitor is really exciting because it’s finally overcome that hurdle.”

Researchers report their experimental approach would also target KRAS G12C, however, it would target many other more common mutations in the gene as well. Pecot’s lab will use the grant to study which mutations are most effectively targeted by their potential therapy, delivery methods for the treatment and the potential toxicity.

Pecot’s lab is currently investigating a novel delivery platform they’ve developed to introduce EFTX-001 specifically to cancer cells. Pecot has applied for international patent protection for RNAi approaches to target a broad range of KRAS mutations and recently founded Enfuego Therapeutics Inc. to further develop RNAi-based cancer therapeutics.

The project is supported by the N.C. Biotechnology Center’s Translational Research Grants, which support potential commercial applications, or initiate early commercial development of university-held life science inventions. To receive the award, the technology must have the potential to solve a real-world problem as a commercial product in the life science sector.

Conflicts of interest: Pecot has equity interest in Enfuego Therapeutics Inc., a company he founded.