Orr Brent A
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Cancer Res. 2025 Jan 15;85(2):195-196. doi: 10.1158/0008-5472.CAN-24-3599.
Mouse models that faithfully represent the biology of human brain tumors are critical tools for unraveling the underlying tumor biology and screening for potential precision therapies. This is especially true of rare tumor types, many of which have correspondingly few xenograft or cell lines available. Although our understanding of the specific biological pathways driving cancer has improved significantly, identifying the appropriate progenitor populations to drive oncogenic processes represents a significant barrier to efficient mouse model production. In this issue of Cancer Research, Jessa and colleagues developed an innovative transcription factor fingerprinting method to map the cellular origin of central nervous system neuroblastoma, FOXR2-activated to medial ganglionic eminence-derived interneurons, which could then be efficiently targeted in the developing mouse brain using in utero electroporation. This approach serves as a blueprint for investigating other rare pediatric brain tumors, potentially accelerating progress toward the development of mouse models and identification of effective therapies. See related article by Jessa et al., p. 231.
能够忠实地反映人类脑肿瘤生物学特性的小鼠模型,是揭示潜在肿瘤生物学机制和筛选潜在精准疗法的关键工具。对于罕见肿瘤类型而言尤其如此,其中许多相应地可用的异种移植模型或细胞系很少。尽管我们对驱动癌症的特定生物学途径的理解有了显著提高,但确定驱动致癌过程的合适祖细胞群体仍是高效生产小鼠模型的重大障碍。在本期《癌症研究》中,杰萨及其同事开发了一种创新的转录因子指纹图谱方法,以确定中枢神经系统神经母细胞瘤的细胞起源,即FOXR2激活的内侧神经节隆起衍生的中间神经元,然后可通过子宫内电穿孔在发育中的小鼠脑中对其进行有效靶向。这种方法为研究其他罕见的儿童脑肿瘤提供了蓝图,有可能加速小鼠模型开发和有效疗法识别方面的进展。见杰萨等人的相关文章,第231页。