Identifying and Targeting the Drivers of Pediatric Brain Tumors

项目总结 髓母细胞瘤是儿童最常见的恶性脑肿瘤。尽管积极的治疗已经 虽然预后有所改善，但仍有许多患者死于疾病，幸存者遭受严重的长期副作用。 从治疗中脱身。因此，更安全、更有效的治疗方法至关重要。在我们之前的研究中，我们 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，识别关键 肿瘤启动和维持的调节剂，并发现可能对治疗肿瘤有效的药物 疾病。尽管我们在过去几年中取得了重要进展，但仍有一些关键问题 仍未得到解答的问题。在未来的几年里，我们将利用这些模型和方法 我们已经发展到：(1)确定驱动因素并为最致命的髓母细胞瘤建立模型；(2) 揭示软脑膜转移的分子机制，寻找新的靶向策略 转移性疾病；(3)利用原发患者肿瘤作为发现新疗法的平台；以及(4)确定 调节髓母细胞瘤免疫反应的机制。我们研究的总体目标是获得一个 加深对髓母细胞瘤生物学的了解，并利用这些信息开发更有效的方法 去接受治疗。尽管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.