University of Connecticut School of Medicine, Farmington, CT, USA.
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Cancer Control. 2024 Jan-Dec;31:10732748241270564. doi: 10.1177/10732748241270564.
Despite improvements in patient outcomes, pediatric cancer remains a leading cause of non-accidental death in children. Recent genetic analysis of patients with pediatric cancers indicates an important role for both germline genetic predisposition and cancer-specific somatic driver mutations. Increasingly, evidence demonstrates that the developmental timepoint at which the cancer cell-of-origin transforms is critical to tumor identity and therapeutic response. Therefore, future therapeutic development would be bolstered by the use of disease models that faithfully recapitulate the genetic context, cell-of-origin, and developmental window of vulnerability in pediatric cancers. Human stem cells have the potential to incorporate all of these characteristics into a pediatric cancer model, while serving as a platform for rapid genetic and pharmacological testing. In this review, we describe how human stem cells have been used to model pediatric cancers and how these models compare to other pediatric cancer model modalities.
尽管患者的预后得到了改善，但儿科癌症仍然是导致儿童非意外死亡的主要原因。最近对儿科癌症患者的基因分析表明，种系遗传易感性和癌症特异性体细胞驱动突变都起着重要作用。越来越多的证据表明，癌症起源细胞发生转化的发育时间点对于肿瘤特征和治疗反应至关重要。因此，未来的治疗开发将得益于使用能够真实再现儿科癌症遗传背景、起源细胞和易损性发育窗口的疾病模型。人类干细胞有可能将所有这些特征纳入儿科癌症模型，同时作为快速基因和药物测试的平台。在这篇综述中，我们描述了人类干细胞如何用于儿科癌症模型，以及这些模型与其他儿科癌症模型方式的比较。
