Usai Alice, Di Franco Gregorio, Colucci Patrizia, Pollina Luca Emanuele, Vasile Enrico, Funel Niccola, Palmeri Matteo, Dente Luciana, Falcone Alfredo, Morelli Luca, Raffa Vittoria
Department of Biology, University di Pisa, S.S. 12 Abetone e Brennero 4, 56127 Pisa, Italy.
Department of Traslational Research and New Technologies in Medicine and Surgery, General Surgery Unit, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.
Cancers (Basel). 2020 Mar 13;12(3):677. doi: 10.3390/cancers12030677.
Animal "avatars" and co-clinical trials are being developed for possible use in personalized medicine in oncology. In a co-clinical trial, the cancer cells of the patient's tumor are xenotransplanted into the animal avatar for drug efficacy studies, and the data collected in the animal trial are used to plan the best drug treatment in the patient trial. Zebrafish have recently been proposed for implementing avatar models, however the lack of a general criterion for the chemotherapy dose conversion from humans to fish is a limitation in terms of conducting co-clinical trials. Here, we validate a simple, reliant and cost-effective avatar model based on the use of zebrafish embryos. By crossing data from safety and efficacy studies, we found a basic formula for estimating the equivalent dose for use in co-clinical trials which we validated in a clinical study enrolling 24 adult patients with solid cancers (XenoZ, NCT03668418).
动物“化身”和联合临床试验正在开发中,可能用于肿瘤学的个性化医疗。在联合临床试验中,将患者肿瘤的癌细胞异种移植到动物化身中进行药物疗效研究,动物试验收集的数据用于规划患者试验中的最佳药物治疗方案。最近有人提议使用斑马鱼来建立化身模型,然而,缺乏从人类到鱼类化疗剂量转换的通用标准是进行联合临床试验的一个限制因素。在此,我们基于斑马鱼胚胎验证了一种简单、可靠且经济高效的化身模型。通过交叉安全和疗效研究的数据,我们发现了一个用于估计联合临床试验等效剂量的基本公式,并在一项纳入24名成年实体癌患者的临床研究(XenoZ,NCT03668418)中进行了验证。