Targeting KRAS Mutations for Ultra-Personalized Treatments in Colon Cancer

Researchers at Fox Chase Cancer Center have uncovered a significant mutation within a common oncogene known as KRAS, which plays a critical role in the development of colon cancer. Their study reveals that this mutation could be a promising target for highly individualized therapies. The study, published in Cell Reports under the title "KRAS G12V Mutation-Selective Requirement for ACSS2 in Colorectal Adenoma Formation," highlights how specific mutations in the KRAS gene influence cancer progression and treatment resistance.

KRAS is one of the earliest identified oncogenes linked to various cancers, particularly colorectal cancer, where its mutations are associated with poorer prognosis and increased resistance to conventional treatments. Although previous assumptions suggested that different mutations of KRAS had similar effects, recent research has demonstrated that specific variants possess unique functional properties.

In the new study, scientists employed CRISPR gene editing to create mouse colon cells containing different KRAS mutations. They observed distinct differences in how these mutations influenced cellular functions. Notably, the G12V mutation in KRAS exhibited a unique way of synthesizing acetyl-CoA, an essential metabolite involved in the production of fatty acids and proteins. Unlike other variants, KRAS G12V utilized a different enzyme to produce acetyl-CoA, making it particularly vulnerable to targeted disruption.

Blocking the enzyme specific to KRAS G12V’s pathway successfully hindered its ability to produce acetyl-CoA, opening the door for highly targeted therapeutic strategies. These findings, validated through experiments in cell lines and mouse models, suggest that therapies designed to inhibit this enzyme could selectively suppress tumors harboring this mutation.

This research marks a significant step toward the development of ultra-personalized cancer treatments, aiming to tailor therapies to the specific genetic makeup of an individual’s tumor. Future studies will explore the potential of this approach in human cells and organoids, as well as in pancreatic and lung cancers where KRAS mutations are also prevalent. Such advancements could profoundly improve outcomes for patients with KRAS-driven cancers.

For more information, see the full study: Konstantin Budagyan et al, "KRAS G12V mutation-selective requirement for ACSS2 in colorectal adenoma formation," Cell Reports (2025). Source: Medical Xpress.