UC study explores new treatments for mutated colorectal cancers

UC study explores new treatments for mutated colorectal cancers

Researcher receives NCI grant to test combinations that target KRAS, HER3 genes

An estimated 53,000 Americans died of colorectal cancer in 2024, and diagnoses and deaths in patients under 50 continue.

Approximately 41% of all colorectal cancers have a mutation in the KRAS gene. Although the first KRAS-targeting drug was approved by the Food and Drug Administration in 2021, mutations in cancer cells and resistance to new treatments create a need for new approaches that combine other treatments with the new KRAS drugs.

The University of Cincinnati Cancer Center's Joan Garrett, PhD, has received a two-year, $162,000 National Cancer Institute grant to study a new combination approach to treat KRAS-mutated colorectal cancers.

Garrett explained that KRAS and the HER family are some of the most frequently altered genes that help cancer cells grow and evade cell death. Prior research from the Garrett lab found that when colorectal cancer cells are treated with KRAS inhibitors, HER3 levels increase to help the cells survive.

"So co-targeting this HER family with KRAS is the goal of the project," said Garrett, a Cancer Center researcher and associate professor in UC's James L. Winkle College of Pharmacy.

The grant will fund research using patient-derived xenografts, animal models with human tumor samples.

Joan Garrett, PhD, said a combination targeted therapy could lead to better outcomes and less toxicity for patients. Photo/Colleen Kelley/UC Marketing + Brand

"The advantage of these is they're really going to closely recapitulate what's happening in a human versus cell lines, which are grown on plastic," Garrett said. "We have these patient-derived xenografts from colorectal cancers and we are cotreating them with KRAS inhibitors plus different HER3 targeted agents to see if we get better inhibition than just single agent KRAS inhibitors."

If the combination KRAS and HER3 treatments are found safe and effective, Garrett said they could be used as options for patients whose cancer has already spread.

"The goal here is to extend and have better outcomes for patients, extend their lives and have less toxic treatments, because these targeted agents are going to be less toxic compared to nonspecific chemotherapy," she said.

Garrett said it is an exciting time to be working in colorectal cancer research, as scientists develop more targeted and effective treatments.

"The fact that in the past five years we have gotten FDA-approved drugs that target KRAS inhibitors is a game changer, and there's a lot of exciting clinical trials that are ongoing," she said. "These new treatments are really showing a lot of promise that will extend the lives of patients."

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Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number 1R03CA304041-0. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Featured photo at top of Garrett working in the lab. Photo/Colleen Kelley/UC Marketing + Brand.

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