The Efficacy of Using Patient-Derived Organoids to Predict Treatment Response in Colorectal Cancer

SIMPLE SUMMARY: Colorectal cancer is the third most commonly diagnosed cancer. Patients may receive chemotherapy, targeted therapy, immunotherapy, radiotherapy, and/or surgery. However, not all patients will benefit from each available treatment option. There has been rising interest in personalised medicine, which refers to tailoring treatment plans to the unique characteristics of each patient’s cancer. Patient-derived tumour organoids are three-dimensional models of patients’ cancer cells which can be tested for sensitivity to various treatment options in the laboratory. This review summarises studies which have explored whether the organoid’s sensitivity in the laboratory corresponds to the patient’s response in the clinic. Tumour organoids are promising models for personalised medicine in the context of selecting chemotherapy and radiotherapy options. Further advancements in organoid technology are required for testing immunotherapy and certain targeted therapy options. Overall, future clinical trials of organoid testing prior to treatment commencement will support the implementation of organoid-based personalised medicine in the clinic. ABSTRACT: Colorectal cancer is an important cause of morbidity and mortality worldwide. The current treatment landscape includes chemotherapy, targeted therapy, immunotherapy, radiotherapy, and surgery. A key challenge to improving patient outcomes is the significant inter-patient heterogeneity in treatment response. Tumour organoids derived from the patients’ tumours via surgically resected or endoscopically biopsied tissue, have emerged as promising models for personalised medicine. This review synthesises the findings, to date, of studies which have explored the efficacy of ex vivo organoid sensitivity testing for predicting treatment response. Most studies have focused on predicting the response to standard-of-care radiotherapy and chemotherapy options. There is strong evidence to support organoid sensitivity testing of ionising radiation, 5-fluorouracil, and irinotecan, and to a lesser extent, oxaliplatin and TAS-102. Fewer studies have used organoids to identify patients who are likely to benefit from novel treatment options that otherwise remain in clinical trials. This review also summarises recent advancements in organoid culture to include non-epithelial components of the tumour microenvironment, to allow testing of immunotherapy and certain targeted therapy options. Overall, further prospective trials will support the implementation of organoid-based personalised medicine for colorectal cancer patients in the future.