SPORE in Brain Cancer

德克萨斯大学安德森癌症中心(UTMDACC)的目标是开发一个强有力的转化研究计划，重点是基于药物组合、基于分子的诊断和治疗监测的创新治疗，通过这些计划将对恶性脑瘤患者的护理产生重大影响。UTMDACC已将消除脑肿瘤作为优先事项，并通过建立脑瘤中心和多学科研究计划来支持跨多个部门的培训和研究，包括神经肿瘤学、神经外科、神经病理学、诊断成像、放射肿瘤学、流行病学、分子治疗学、分子遗传学、分子生物学、儿科和统计学，从而在这一目标上进行了重大投资。在这种支持下，我们成功地组织了一个高效和富有成效的基础设施，构成了这一孢子的基础。这一应用中的转化性研究基于对脑肿瘤分子基础的最新见解，旨在将这些发现转化为创新的方法，以改进分子诊断，以便患者接受最有可能使他们受益的治疗，允许及早评估靶向治疗的反应，并建立基于溶瘤病毒和小分子信号转导抑制剂的新的有效治疗方法。四个项目的重点介绍如下： 项目1：在临床上测试一种靶向溶瘤腺病毒Delta-24-RGD，并通过与替莫唑胺联合和与间充质干细胞联合使用来改进它。 项目二：临床试验PI3K抑制剂PX-866，并在此基础上开发合理的联合治疗方法。 项目3：开发一种分子生物标记物小组，能够识别不太可能从标准治疗中受益的患者，在RTOG-0525临床试验中对800多名患者进行测试，并确定耐药肿瘤治疗的新靶点，以支持新的治疗开发。 项目4：探索神经母细胞瘤患者神经认知和临床结局的遗传预测因子。 五个核心(行政、病理和组织采购、生物统计学、临床和动物)将支持项目、职业发展计划和发展研究计划。我们必须积极开展转化性研究，这一建议体现在为脑癌患者开发更有效的方法；对于这一患者群体，没有有效的治疗方法，这一孢子保证了UTMDACC脑瘤研究计划的所有资源，以及整个机构的大量资源，将用于这一重要的公共卫生问题。

The objective of The University of Texas M. D. Anderson Cancer Center (UTMDACC) SPORE in Brain Cancer is to develop a robust translational research program with an emphasis on innovative treatments based on combinations of agents, molecularly-based diagnosis, and therapy monitoring, through which significant impact on the care of patients with malignant brain tumors will be achieved. UTMDACC has established the elimination of brain tumors as a priority and has made significant investments in this goal through establishment of a Brain Tumor Center and a Multidisciplinary Research Program to support training and research across several departmental boundaries, including neuro-oncology, neuro-surgery, neuro-pathology, diagnostic imaging, radiation oncology, epidemiology, molecular therapeutics, molecular genetics, molecular biology, pediatrics, and statistics. With this support, we have successfully organized an efficient and productive infrastructure that forms the basis for this SPORE. The translational research in this application is based on recent insights into the molecular basis of brain tumors and aims to translate these findings into innovative approaches to improve molecular diagnosis so that patients receive the therapy most likely to be benefit them, permit early evaluation of response to targeted treatment, and establish new and effective treatments based on oncolytic viruses and small molecule signal transduction inhibitors. The focus of the four Projects is described below: Project 1: Test a targeted oncolytic adenovirus, Delta-24-RGD in the clinic, and improve it by combining it with temozolomide and by delivery with mesenchymal stem cells. Project 2: Test PI3K inhibitor PX-866 in the clinic and develop rational combination therapies based on it. Project 3: Develop a molecular biomarker panel capable of identifying patients not likely to benefit from standard therapy, test it in the RTOG-0525 clinical trial with over 800 patients, and identify novel targets in the treatment of resistant tumors to support new therapy development. Project 4: Explore genetic predictors of neurocognitive and clinical outcome in glioblastoma patients. Five Cores (Administrative, Pathology and Tissue Procurement, Biostatistics, Clinical and Animal) will support the Projects, Career Development Program, and Developmental Research Program. It is imperative that we aggressively undertake translational research, as is embodied in this proposal to develop more effective approaches for patients with brain cancer; there are no effective treatment approaches for this patient population, and this SPORE guarantees that all of the resources of the UTMDACC Brain Tumor Research Program, as well as the considerable resources of the entire institution, will be brought to bear on this important public health problem.