Innovative Approach Offers New Hope for KRAS-Mutated Colon Cancer Treatment

Recent research by the Center for Cancer Research at the Medical University of Vienna has unveiled an overlooked yet promising strategy for combatting KRAS-mutated colon cancer, one of the most challenging forms of cancer to treat. Traditionally, KRAS mutations are associated with limited treatment options, as they often render targeted therapies ineffective. However, the latest findings, published in EMBO Molecular Medicine, suggest that targeting the epidermal growth factor receptor (EGFR) signaling pathway could be effective even in cases with KRAS mutations.

First author Dana Krauß explained that EGFR, a receptor on the cell surface, previously was deemed irrelevant as a therapeutic target in KRAS-mutated tumors. This assumption has now been challenged. Using tumor organoids—miniature, lab-grown tumors derived from colon cancer cells—researchers demonstrated that blocking EGFR significantly alters cancer cell metabolism. The removal of EGFR not only impacts sugar and amino acid processing but also activates gene signatures linked to longer survival in patients with KRAS mutations.

Further analysis showed that inhibiting EGFR slows down glycolysis, the process by which cells break down sugar for energy. Tumor cells were observed to switch their energy source to glutamine, indicating a fundamental change in their metabolism. Interestingly, this intervention also activates the Wnt signaling pathway, known for its role in colon cancer development, and influences stem cell activity.

A key player in these processes is the gene Smoc2, which rewires cell metabolism and activates new signaling networks. Data from patient cohorts revealed that higher activity of this gene is associated with better outcomes in KRAS-mutated colorectal cancer.

These findings challenge current medical practices, which often exclude patients with KRAS mutations from receiving EGFR-targeted therapies. The research suggests that combination therapies targeting both EGFR and KRAS could be a more effective approach. Although clinical trials are still needed, these insights highlight a new avenue for improving treatment options for this aggressive cancer type.

Maria Sibilia, head of the Center for Cancer Research, emphasizes the importance of questioning existing assumptions in cancer therapy. This breakthrough adds to the growing understanding that personalized treatments based on cellular metabolism and signaling pathways could revolutionize how KRAS-mutated colon cancer is managed.

Source: https://medicalxpress.com/news/2025-05-overlooked-strategy-kras-mutated-colon.html