Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer

Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors. Chemoradiation responses in patients are highly matched to RCO responses, with 84.43% accuracy, 78.01% sensitivity, and 91.97% specificity. These data imply that PDOs predict LARC patient responses in the clinic and may represent a companion diagnostic tool in rectal cancer treatment. [Display omitted] •Living biobank with 80 tumor organoids was derived from treatment-naive CRC patients•Tumor organoids recapitulate histological and genetic features of original tumors•Interpatient variability in the PDO response to chemoradiation treatments•PDOs can predict locally advanced rectal cancer patient responses in the clinic Yao et al. generated a patient-derived organoid (PDO) biobank from patients with locally advanced rectal cancer (LARC) and reported that organoids had similar molecular profiles to those of the patient tumor and that PDOs can predict LARC patient chemoradiation responses, reinforcing their value as a companion diagnostic tool in LARC treatment.