Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients

By S. Ooft, F. Weeber, K. Dijkstra, C. McLean, S. Kaing, E. van Werkhoven, L. Schipper, L. Hoes, D. Vis, J. van de Haar and 13 more. Science Translational Medicine, 2019

658 citations recorded by the source corpus.

Tumor organoids from individual patients with metastatic colorectal cancer can help predict response to irinotecan with or without 5-fluorouracil. Dishing out treatment recommendations The number of treatment options for cancer patients keeps expanding, but it remains difficult to predict which tumors will be sensitive to which treatments. As a result, most patients receive treatment according to standardized protocols. With this approach, some patients respond to treatment, but others only experience side effects. To help address this situation, Ooft et al. developed a method of testing drugs in patient-derived organoids, biopsy-derived cells from individual patients grown in a dish. In a clinical study, the responses of organoids to irinotecan correlated with patients’ responses to the drug, suggesting that organoids could help avoid giving irinotecan to patients who would not benefit. There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy. Our PDO test predicted response of the biopsied lesion in more than 80% of patients treated with irinotecan-based therapies without misclassifying patients who would have benefited from treatment. This correlation was specific to irinotecan-based chemotherapy, however, and the PDOs failed to predict outcome for treatment with 5-fluorouracil plus oxaliplatin. Our data suggest that PDOs could be used to prevent cancer patients from undergoing ineffective irinotecan-based chemotherapy.

Subfields: Oncology

View Paper: https://www.semanticscholar.org/paper/e893d58c6ec8871534f8b094012e6e355ed26587