Background Colorectal organoids are three-dimensional cultures of cells, sometimes termed “mini-guts” that can be derived from healthy patient tissues and tumours. Organoids recapitulate the features of the tissue from which they are derived, and therefore serve as an innovative tool for cancer research. In particular, patient-derived tumour organoids have potential for use in pre-clinical drug testing and the development of personalised cancer medicine.
Aim Establish tumour-derived organoids from colorectal cancer (CRC) patients for the development of drug response assays, testing routine cancer therapies including radiation therapy and chemotherapy drugs used for the treatment of CRC. This data will be compared to patient outcomes recorded on the Cabrini Monash University Department of Surgery (CMUDS) Colorectal Neoplasia database. Ultimately, this project aims to develop a routine pre-clinical test that can predict treatment outcomes for CRC patients, before they undergo therapy.
Methods Collect healthy tissue and tumour from CRC patients undergoing biopsy or tissue resection to establish organoid cultures. Organoids are tested in dose-response assays with radiation therapy and an array of chemotherapy drugs. Sensitivity to treatment is measured by the ability of the organoids survive and proliferate.
Results We have successfully established tumour-derived organoids from approximately 80% of patient samples. A number of drug assays treating tumour organoids with chemotherapy drugs, fluorouracil (5-FU) and oxaliplatin, have been performed. In addition, we have undertaken preliminary studies for radiation treatment of tumour organoids. All drug and radiation assays are currently performed in a blinded manner, however the responses observed in the organoid cultures will be correlated (where possible) to patient outcomes recorded in the CMUDS database. This process will allow us to validate the effectiveness and accuracy of this system for predicting sensitivity to drug and radiation treatment for each patient.
Conclusion Patient-derived tumour organoids are a powerful tool for cancer research and have the potential to be utilised pre-clinically to predict treatment outcomes in CRC patients.