Li Zhiqin, Langhans Sigrid A
Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
Front Oncol. 2021 Apr 1;11:620831. doi: 10.3389/fonc.2021.620831. eCollection 2021.
After leukemia, tumors of the brain and spine are the second most common form of cancer in children. Despite advances in treatment, brain tumors remain a leading cause of death in pediatric cancer patients and survivors often suffer from life-long consequences of side effects of therapy. The 5-year survival rates, however, vary widely by tumor type, ranging from over 90% in more benign tumors to as low as 20% in the most aggressive forms such as glioblastoma. Even within historically defined tumor types such as medulloblastoma, molecular analysis identified biologically heterogeneous subgroups each with different genetic alterations, age of onset and prognosis. Besides molecularly driven patient stratification to tailor disease risk to therapy intensity, such a diversity demonstrates the need for more precise and disease-relevant pediatric brain cancer models for research and drug development. Here we give an overview of currently available and pediatric brain tumor models and discuss the opportunities that new technologies such as 3D cultures and organoids that can bridge limitations posed by the simplicity of monolayer cultures and the complexity of models, bring to accommodate better precision in drug development for pediatric brain tumors.
白血病之后，脑和脊柱肿瘤是儿童中第二常见的癌症形式。尽管治疗取得了进展，但脑肿瘤仍然是儿科癌症患者死亡的主要原因，幸存者往往会遭受治疗副作用带来的终身后果。然而，5年生存率因肿瘤类型而异，从较良性肿瘤的90%以上到胶质母细胞瘤等最具侵袭性形式的低至20%不等。即使在历史上定义的肿瘤类型如髓母细胞瘤中，分子分析也确定了生物学上异质的亚组，每个亚组都有不同的基因改变、发病年龄和预后。除了通过分子驱动的患者分层来根据治疗强度调整疾病风险外，这种多样性表明需要更精确且与疾病相关的儿科脑癌模型用于研究和药物开发。在这里，我们概述了当前可用的儿科脑肿瘤模型，并讨论了诸如3D培养和类器官等新技术带来的机遇，这些新技术可以弥补单层培养的简单性和动物模型的复杂性所带来的局限性，从而在儿科脑肿瘤药物开发中实现更高的精准度。
