Plocabulin displays strong cytotoxic activity in a personalized colon cancer patient-derived 3D organoid assay

This article belongs to the Special Issue 3D Cell Culture Based on Marine Resources.Plocabulin is a novel microtubule-disrupting antitumor agent of marine origin that is currently undergoing phase II clinical trials. Plocabulin has potent antiproliferative and antiangiogenic actions in carcinoma cell lines and has antitumor activity in xenografted mice. Here, we used three-dimensional (3D) tumor organoids derived from three colorectal cancer (CRC) patients to study the effect of plocabulin in a personalized assay system that ensures dose dependence and high reproducibility. The cytotoxicity of plocabulin was an order of magnitude higher than that of the active irinotecan derivative SN38 (7-ethyl-10-hydroxy-camptothecin) in tumor organoids at different passages. Moreover, plocabulin maintained its strong cytotoxic activity in wash-out experiments, in which a short pulse treatment of tumor organoids was as efficient as continuous treatment. Our data show that plocabulin has a very potent cytotoxic action in CRC patient-derived tumor organoids, supporting ongoing clinical trials with plocabulin and the use of organoid assays to provide personalized validation of antitumor drugs.This study was supported by grants SAF2016-76377-R (AEI/FEDER, UE), SAF2017-90604-REDT (Nurcamein) and ISCIII-CIBERONC CB16/12/00273 (to A.M.) from the Spanish Ministry of Science, Innovation and Universities.Peer reviewe