Identifying and Targeting the Drivers of Pediatric Brain Tumors

项目摘要 髓母细胞瘤是儿童最常见的恶性脑肿瘤。尽管积极的治疗 尽管结果有所改善，但许多患者仍然死于疾病，幸存者遭受严重的长期副作用 从治疗中恢复过来因此，更安全和更有效的治疗方法至关重要。在我们以前的研究中， 他们创造了新的髓母细胞瘤动物模型，并用它们来定义起源细胞，确定关键细胞， 肿瘤起始和维持的调节剂，并揭示可能有效治疗肿瘤的药物。 疾病尽管我们在过去几年中取得了重大进展，但仍存在一些关键问题。 仍然没有答案的问题。在未来几年，我们将利用这些模式和方法， 我们已经发展到：（1）识别驱动因素并为最致命的髓母细胞瘤形式创建模型;（2） 揭示软脑膜转移的分子机制，并找到新的靶向策略 转移性疾病;（3）使用原发性患者肿瘤作为发现新疗法的平台;以及（4）识别 调节对髓母细胞瘤的免疫反应的机制。我们研究的总体目标是获得 更深入地了解髓母细胞瘤生物学，并利用这些信息开发更有效的方法 接受治疗虽然这些研究是雄心勃勃的，但如果我们要改变人们的生活，它们是必不可少的。 患有这种毁灭性疾病的儿童。

PROJECT SUMMARY Medulloblastoma is the most common malignant brain tumor in children. Although aggressive treatments have improved outcomes, many patients still die of their disease, and survivors suffer severe long-term side effects from the therapy. Thus, safer and more effective approaches to therapy are critical. In our previous studies we have created new animal models of medulloblastoma and used them to define cells of origin, identify key regulators of tumor initiation and maintenance, and uncover agents that may be effective for therapy of the disease. Although we have made important strides over the last few years, there are a number of critical questions that remain unanswered. In the coming years, we will take advantage of the models and approaches we have developed to: (1) Identify drivers and create models for the deadliest forms of medulloblastoma; (2) Uncover the molecular mechanisms of leptomeningeal metastasis, and find novel strategies for targeting metastatic disease; (3) Use primary patient tumors as a platform to discover new therapies; and (4) Identify mechanisms that regulate immune responses to medulloblastoma. The overall goal of our research is to gain a deeper understanding of medulloblastoma biology and use this information to develop more effective approaches to therapy. Although these studies are ambitious, they are essential if we are to make a difference in the lives of children with this devastating disease.