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Promising Therapeutic Option for Overcoming Cetuximab Resistance in Colorectal Cancer Stem Cells: Inhibition of the AURKA/YAP1 Axis – British Journal of Cancer

Colorectal cancer is one of the most common types of cancer worldwide, with over 1.8 million new cases diagnosed each year. While advancements in treatment options have improved survival rates, resistance to certain therapies remains a significant challenge in managing the disease. One such therapy that has shown promise in treating colorectal cancer is cetuximab, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR).

However, a significant number of patients develop resistance to cetuximab, leading to disease progression and poorer outcomes. Recent research published in the British Journal of Cancer has identified a potential therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells: inhibition of the AURKA/YAP1 axis.

The study, conducted by a team of researchers from various institutions, including the University of Oxford and the University of Cambridge, investigated the role of the AURKA/YAP1 axis in mediating resistance to cetuximab in colorectal cancer stem cells. Aurora kinase A (AURKA) is a protein that plays a crucial role in cell division, while Yes-associated protein 1 (YAP1) is a transcriptional co-activator that regulates gene expression.

The researchers found that the AURKA/YAP1 axis was upregulated in cetuximab-resistant colorectal cancer stem cells compared to sensitive cells. Inhibition of AURKA or YAP1 using specific inhibitors or RNA interference sensitized resistant cells to cetuximab, leading to decreased cell viability and increased apoptosis.

Furthermore, the researchers demonstrated that targeting the AURKA/YAP1 axis in combination with cetuximab resulted in synergistic effects, suggesting that this approach could potentially overcome resistance to cetuximab in colorectal cancer stem cells.

These findings have important clinical implications for the treatment of colorectal cancer patients who develop resistance to cetuximab. By targeting the AURKA/YAP1 axis, clinicians may be able to enhance the efficacy of cetuximab and improve patient outcomes.

Overall, the study published in the British Journal of Cancer highlights a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells. Further research is needed to validate these findings in clinical trials and determine the optimal treatment strategies for patients with resistant disease.