Department of Cancer Biology, Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM) 28029 Madrid, Spain and University Hospital La Paz Institute for Health Research (IdiPAZ), 28046 Madrid, Spain.
Biomedical Research Networking Centres-Oncology (CIBERONC), 28029 Madrid, Spain.
Mar Drugs. 2019 Nov 19;17(11):648. doi: 10.3390/md17110648.
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.
普乐沙福是一种新型的源自海洋的微管破坏抗肿瘤药物，目前正在进行 II 期临床试验。普乐沙福在癌细胞系中具有很强的抗增殖和抗血管生成作用，并在异种移植小鼠中具有抗肿瘤活性。在这里，我们使用源自三名结直肠癌（CRC）患者的三维（3D）肿瘤类器官来研究普乐沙福在确保剂量依赖性和高重现性的个性化测定系统中的作用。在不同传代的肿瘤类器官中，普乐沙福的细胞毒性比活性伊立替康衍生物 SN38（7-乙基-10-羟基喜树碱）高出一个数量级。此外，普乐沙福在洗脱实验中保持其强大的细胞毒性活性，其中肿瘤类器官的短暂脉冲处理与连续处理一样有效。我们的数据表明，普乐沙福在 CRC 患者来源的肿瘤类器官中具有很强的细胞毒性作用，支持普乐沙福的正在进行的临床试验以及使用类器官测定法为抗肿瘤药物提供个性化验证。
