October 9, 2019
and oxaliplatin (oxaliplatin Cmax in patients = 3.8 to 10.1 mM; oxaliplatin range in vitro = 0.319 to 200 mM) in patients using a Tecan D300e digital dispenser (31â33)
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. Copyright Š 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Ooft, SN; Weeber, F; Dijkstra, KK; McLean, CM; Kaing, S; van Werkhoven, E; Schipper, L; Hoes, L; Vis, DJ; van de Haar, J; Prevoo, W; Snaebjornsson, P; van der Velden, D; Klein, M; Chalabi, M; Boot, H; van Leerdam, M; Bloemendal, HJ; Beerepoot, LV; Wessels, L; Cuppen, E; Clevers, H; Voest, EE;
Journal: Sci Transl Med