Ornell Kimberly J, Coburn Jeannine M
Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01605 USA.
BMC Biomed Eng. 2019 Dec 20;1:33. doi: 10.1186/s42490-019-0034-8. eCollection 2019.
Despite advances in cancer therapeutics, particularly in the area of immuno-oncology, successful treatment of neuroblastoma (NB) remains a challenge. NB is the most common cancer in infants under 1 year of age, and accounts for approximately 10% of all pediatric cancers. Currently, children with high-risk NB exhibit a survival rate of 40-50%. The heterogeneous nature of NB makes development of effective therapeutic strategies challenging. Many preclinical models attempt to mimic the tumor phenotype and tumor microenvironment. In vivo mouse models, in the form of genetic, syngeneic, and xenograft mice, are advantageous as they replicated the complex tumor-stroma interactions and represent the gold standard for preclinical therapeutic testing. Traditional in vitro models, while high throughput, exhibit many limitations. The emergence of new tissue engineered models has the potential to bridge the gap between in vitro and in vivo models for therapeutic testing. Therapeutics continue to evolve from traditional cytotoxic chemotherapies to biologically targeted therapies. These therapeutics act on both the tumor cells and other cells within the tumor microenvironment, making development of preclinical models that accurately reflect tumor heterogeneity more important than ever. In this review, we will discuss current in vitro and in vivo preclinical testing models, and their potential applications to therapeutic development.
尽管癌症治疗取得了进展，尤其是在免疫肿瘤学领域，但成功治疗神经母细胞瘤（NB）仍然是一项挑战。NB是1岁以下婴儿最常见的癌症，约占所有儿童癌症的10%。目前，高危NB患儿的生存率为40%-50%。NB的异质性使得开发有效的治疗策略具有挑战性。许多临床前模型试图模拟肿瘤表型和肿瘤微环境。以基因小鼠、同基因小鼠和异种移植小鼠形式存在的体内小鼠模型具有优势，因为它们复制了复杂的肿瘤-基质相互作用，是临床前治疗测试的金标准。传统的体外模型虽然通量高，但存在许多局限性。新的组织工程模型的出现有可能弥合体外和体内治疗测试模型之间的差距。治疗方法正从传统的细胞毒性化疗向生物靶向治疗不断发展。这些治疗方法作用于肿瘤细胞和肿瘤微环境中的其他细胞，使得开发能够准确反映肿瘤异质性的临床前模型比以往任何时候都更加重要。在本综述中，我们将讨论当前的体外和体内临床前测试模型及其在治疗开发中的潜在应用。
