Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy.
Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy.
Int J Mol Sci. 2024 May 15;25(10):5394. doi: 10.3390/ijms25105394.
Glioblastoma multiforme (GBM) is a very aggressive and lethal primary brain cancer in adults. The multifaceted nature of GBM pathogenesis, rising from complex interactions between cells and the tumor microenvironment (TME), has posed great treatment challenges. Despite significant scientific efforts, the prognosis for GBM remains very poor, even after intensive treatment with surgery, radiation, and chemotherapy. Efficient GBM management still requires the invention of innovative treatment strategies. There is a strong necessity to complete cancer in vitro studies and in vivo studies to properly evaluate the mechanisms of tumor progression within the complex TME. In recent years, the animal models used to study GBM tumors have evolved, achieving highly invasive GBM models able to provide key information on the molecular mechanisms of GBM onset. At present, the most commonly used animal models in GBM research are represented by mammalian models, such as mouse and canine ones. However, the latter present several limitations, such as high cost and time-consuming management, making them inappropriate for large-scale anticancer drug evaluation. In recent years, the zebrafish () model has emerged as a valuable tool for studying GBM. It has shown great promise in preclinical studies due to numerous advantages, such as its small size, its ability to generate a large cohort of genetically identical offspring, and its rapid development, permitting more time- and cost-effective management and high-throughput drug screening when compared to mammalian models. Moreover, due to its transparent nature in early developmental stages and genetic and anatomical similarities with humans, it allows for translatable brain cancer research and related genetic screening and drug discovery. For this reason, the aim of the present review is to highlight the potential of relevant transgenic and xenograft zebrafish models and to compare them to the traditionally used animal models in GBM research.
胶质母细胞瘤(GBM)是一种非常侵袭性和致命性的成人原发性脑癌。GBM 发病机制的多面性源于细胞与肿瘤微环境(TME)之间的复杂相互作用,这给治疗带来了巨大挑战。尽管科学界做出了巨大努力,但 GBM 的预后仍然非常差,即使在手术、放疗和化疗的强化治疗后也是如此。有效的 GBM 管理仍然需要发明创新的治疗策略。为了正确评估复杂 TME 中肿瘤进展的机制,有必要完成癌症的体外研究和体内研究。近年来,用于研究 GBM 肿瘤的动物模型已经发展起来,实现了高度侵袭性的 GBM 模型,能够提供有关 GBM 发病分子机制的关键信息。目前,GBM 研究中最常用的动物模型是哺乳动物模型,如小鼠和犬类模型。然而,后者存在一些局限性,例如成本高和管理耗时,使其不适合大规模抗癌药物评估。近年来,斑马鱼()模型已成为研究 GBM 的一种有价值的工具。由于其具有许多优点,如体型小、能够产生大量遗传上相同的后代、发育迅速等,因此在临床前研究中显示出巨大的潜力,与哺乳动物模型相比,它可以更有效地管理、进行高通量药物筛选,并且耗时和成本更低。此外,由于其在早期发育阶段的透明性以及与人类在遗传和解剖学上的相似性,它允许进行可转化的脑癌研究以及相关的遗传筛选和药物发现。因此,本综述的目的是强调相关转基因和异种移植斑马鱼模型的潜力,并将其与传统的 GBM 研究动物模型进行比较。