Improved Drug-Response Prediction Model of APC Mutant Colon Cancer Patient-Derived Organoids for Precision Medicine

Abstract

Colorectal cancer is the third most common cancer in the world, with an annual incidence of 2 million cases. The success of first-line chemotherapy plays a crucial role in determining the disease outcome. Therefore, there is an increasing demand for precision medicine to predict drug responses and optimize chemotherapy in order to increase patient survival and reduce the related side effects. Patient-derived organoids have become a popular in vitro screening model for drug-response prediction for precision medicine. However, there is no established correlation between oxaliplatin and drug-response prediction. Here, we suggest that organoid culture conditions can increase resistance to oxaliplatin during drug screening, and we developed a modified medium condition to address this issue. Notably, while previous studies have shown that survivin is a mechanism for drug resistance, our study observed consistent survivin expression irrespective of the culture conditions and oxaliplatin treatment. However, clusterin induced apoptosis inhibition and cell survival, demonstrating a significant correlation with drug resistance. This study’s findings are expected to contribute to increasing the accuracy of drug-response prediction in patient-derived APC mutant colorectal cancer organoids, thereby providing reliable precision medicine and improving patient survival rates.

Keywords

• colorectal cancer
• patient-derived organoids (PDOs)
• oxaliplatin
• precision medicine
• drug response prediction
• first-line chemotherapy