The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is curated by the Board of the European Association for Cancer Research (EACR).
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S.N. Ooft, F. Weeber et al., Science Translational Medicine Vol 11, Issue 513 09 October 2019
“This paper shows that organoids can be used to predict response to chemotherapy.” Alberto Bardelli, EACR President 2018-20
Summary of the findings
Chemotherapy is effective in only a subset of colorectal cancer (CRC) patients, and therefore many patients are treated to no avail while still experiencing toxic side effects. There are currently no good biomarkers that can identify non-responding patients. Patient-derived tumor organoids (PDOs) are three-dimensional cultures of tumor cells derived from individual patients, and CRC PDOs can be established with high efficiency. We therefore carried out a multi-center, prospective, observational clinical study testing the potential of organoids to predict response to chemotherapy. The primary objective was to develop an in vitro test based on PDOs from metastatic lesions to identify non-responders to standard-of-care chemotherapy in CRC. Pre-treatment tumor biopsies were used to establish organoids, and test chemosensitivity to the same treatment that the patient received.
We correctly predicted response of the biopsied lesion for >80% patients treated with irinotecan-based therapies. Importantly, using this test, we did not misclassify any patients who would have benefited from treatment. In contrast, organoids failed to predict response to treatment with 5-fluorouracil and oxaliplatin, indicating that the potential of organoids to predict response to chemotherapy differs between treatment lines.
Future impact of the findings
Our data suggest that there is potential to use PDOs to prevent treatment of patients who are resistant to irinotecan-based therapies. Our findings should be validated in future studies with larger independent patient cohorts.
