CRC-PDOs for personalized chemotherapy

In this study, we describe the feasibility of patient-derived organoids (PDOs) as a preclinical model to predict the response to oxaliplatin-based adjuvant chemotherapy in advanced colorectal cancer (CRC) patients. Oxaliplatin sensitivity was determined in 42 advanced CRC-derived PDOs. According to IC50, these PDOs were classified into the resistant and sensitive subgroups. PDO xenograft tumor model was performed which demonstrated that oxaliplatin-mediated inhibition on tumor growth in mice correlated to the drug sensitivity assessed in PDOs. Furthermore, patients responses to oxaliplatin-based chemotherapy retrospectively paralleled the drug sensitivity determined in PDOs. These results strongly support the notion that PDOs can serve as a platform to predict response to oxaliplatin-based chemotherapy in advanced CRC patients. For personalized chemotherapy, we painted the molecular portraits of these PDOs and identified predictive biomarkers for oxaliplatin responsiveness. By gene signature-based approaches, we identified drugs that may sensitize oxaliplatin response in the resistant PDOs, as demonstrated by the significantly increased potency and efficacy of oxaliplatin. We conclude that PDOs are useful in predicting oxaliplatin response and in designing effective personalized therapy in advanced CRC patients.