Advances of Patient-Derived Organoids in Personalized Radiotherapy

Abstract

Patient-derived organoids (PDO), based on the advanced three-dimensional (3D) culture technology, can provide more relevant physiological and pathological cancer models, which is especially beneficial for developing and optimizing cancer therapeutic strategies. Radiotherapy (RT) is a cornerstone of curative and palliative cancer treatment, which can be performed alone or integrated with surgery, chemotherapy, immunotherapy, or targeted therapy in clinical care. Among all cancer therapies, RT has great local control, safety and effectiveness, and is also cost-effective per life-year gained for patients. It has been reported that combing RT with chemotherapy or immunotherapy or radiosensitizer drugs may enhance treatment efficacy at faster rates and lower cost. However, very few FDA-approved combinations of RT with drugs or radiosensitizers exist due to the lack of accurate and relevant preclinical models. Meanwhile, radiation dose escalation may increase treatment efficacy and induce more toxicity of normal tissue as well, which has been studied by conducting various clinical trials, very expensive and time-consuming, often burdensome on patients and sometimes with controversial results. The surged PDO technology may help with the preclinical test of RT combination and radiation dose escalation to promote precision radiation oncology, where PDO can recapitulate individual patient' tumor heterogeneity, retain characteristics of the original tumor, and predict treatment response. This review aims to introduce recent advances in the PDO technology and personalized radiotherapy, highlight the strengths and weaknesses of the PDO cancer models, and finally examine the existing RT-related PDO trials or applications to harness personalized and precision radiotherapy.

Keywords: patient-derived organoid (PDO); patient-derived xenograft (PDX); personalized medicine; radiosensitizer; radiotherapy.