Investigations of cancer biology and screening of potential therapeutics for efficacy and safety begin in the preclinical laboratory setting. A staple of most basic research in cancer involves the use of tissue culture plates, on which immortalized cell lines are grown in monolayers. However, this practice has been in use for over six decades and does not account for vital elements of the tumor microenvironment that are thought to aid in initiation, propagation, and ultimately, metastasis of cancer. Furthermore, information gleaned from these techniques does not always translate to animal models or, more crucially, clinical trials in cancer patients. Osteosarcoma (OS) and Ewing sarcoma (ES) are the most common primary tumors of bone, but outcomes for patients with metastatic or recurrent disease have stagnated in recent decades. The unique elements of the bone tumor microenvironment have been shown to play critical roles in the pathogenesis of these tumors and thus should be incorporated in the preclinical models of these diseases. In recent years, the field of tissue engineering has leveraged techniques used in designing scaffolds for regenerative medicine to engineer preclinical tumor models that incorporate spatiotemporal control of physical and biological elements. We herein review the clinical aspects of OS and ES, critical elements present in the sarcoma microenvironment, and engineering approaches to model the bone tumor microenvironment.

中文翻译：

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骨肉瘤的肿瘤微环境和致病信号传导建模。

癌症生物学的研究以及潜在治疗方法有效性和安全性的筛选始于临床前实验室环境。大多数癌症基础研究的主要内容涉及使用组织培养板，永生化细胞系在其上单层生长。然而，这种做法已经使用了六十多年，并且没有考虑到肿瘤微环境中被认为有助于癌症发生、传播和最终转移的重要元素。此外，从这些技术中收集的信息并不总能转化为动物模型，或更重要的是，转化为癌症患者的临床试验。骨肉瘤（OS）和尤文肉瘤（ES）是最常见的原发性骨肿瘤，但近几十年来，转移性或复发性疾病患者的预后停滞不前。骨肿瘤微环境的独特元素已被证明在这些肿瘤的发病机制中发挥着关键作用，因此应该纳入这些疾病的临床前模型中。近年来，组织工程领域利用再生医学支架设计技术来设计临床前肿瘤模型，其中结合了物理和生物元素的时空控制。我们在此回顾了 OS 和 ES 的临床方面、肉瘤微环境中存在的关键元素以及骨肿瘤微环境建模的工程方法。