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中文摘要
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德克萨斯大学安德森癌症中心(UTMDACC)脑癌SPORE的目标是开发一个强大的转化研究项目,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,通过这些治疗将对恶性脑肿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,并通过建立脑肿瘤中心和多学科研究项目为这一目标进行了重大投资,以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,儿科学和统计学。在这种支持下,我们已经成功地组织了一个高效和富有成效的基础设施,形成了这个孢子的基础。本应用程序的转化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改进分子诊断的创新方法,以便患者接受最有可能对他们有益的治疗,允许早期评估对靶向治疗的反应,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。四个项目的重点如下:
英文摘要
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.
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Targeting the PI3K Pathway in Malignant Glioma
SPORE in Brain Cancer
SPORE in Brain Cancer
Targeting the PI3 pathway in Gliomas with PI3 inhibitors and rational combination
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