SPORE in Brain Cancer

脑癌中的孢子

• 批准号: 8735849
• 负责人: FREDERICK F LANG
• 金额: $ 206.74万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8735849
• 关键词: Adenoviruses; Aftercare; Animal Model; Animals; Autophagocytosis; Award; Back; Bioinformatics; Biological; Biological Markers; Biological Response Modifier Therapy; Bone Marrow Stem Cell; Brain; Brain Neoplasms; Caring; Cell Line; Central Nervous System Neoplasms; Clinic; Clinical; Clinical Trials; Collaborations; Collection; Combined Modality Therapy; Development; Diagnosis; Diagnostic; Diagnostic tests; Funding; Genes; Glioblastoma; Glioma; Goals; Grant; Human; Immune; Immunosuppression; Immunotherapy; Life; Malignant Glioma; Malignant neoplasm of brain; Medicine; Mission; Molecular; Oncolytic; Oncolytic viruses; Outcome; Pathology; Patient Care; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Phase III Clinical Trials; Primary Brain Neoplasms; Prognostic Marker; Radiation Therapy Oncology Group; Radiosurgery; Records; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; STAT3 gene; Science; Specimen; Stem cells; Testing; Therapeutic; Tissues; Translating; Translational Research; Tumor Stem Cells; University of Texas M D Anderson Cancer Center; Viral; Work; base; bench to bedside; bevacizumab; biobank; cancer diagnosis; career development; chemotherapy; combinatorial; cytotoxic; cytotoxicity; design; flexibility; improved; inhibitor/antagonist; multidisciplinary; next generation; novel; novel therapeutic intervention; population based; prognostic; programs; randomized trial; response; success; targeted delivery; temozolomide; tumorigenesis

This MD Anderson Brain Cancer SPORE renewal application builds upon the significant progress achieved in the initial funding period, including the development of novel biological (oncolytic virus, stem cells), targeted (PI3K inhibitors), and immunomodulaton (p-STAT-3 inhibition) therapeutic strategies; as well as the development of biomarkers that inform personalized care of GBM patients. In this renewal, our goal is to capitalize on these prior successes in order to dramatically improve the survival of patients with malignant gliomas. We have established a multidisciplinary, integrated, flexible, and highly translational (bench to bedside and back) research program that aims to discover and rationally test new biologic, targeted, and immunological therapies, and that seeks to develop prognostic and predictive biomarkers that inform individualized approaches to GBM treatment. To achieve our goals we propose four fully translational research projects (3 therapeutic; 1 population-based), all of which incorporate tissue-based clinical trials, and are supported by five Cores: Administrative (A), Pathology and Biorepository (B), Biostatics and Bioinformatics (C), Clinical (D), and Animal (E). The Developmental Research Program (DRP) and Career Development Program (CDP) continue as successful aspects of our SPORE as they encourage novel studies and promote young investigators. The aims of the four projects are to: Project 1: Enhance the efficacy of a novel oncolytic adenovirus, Delta-24-RGD, by combining it with temozolomide, by exploiting autophagy, and by improving delivery using bone marrow stem cells; Project 2: Explore combinatorial targeted strategies based on PISKinase inhibition by elucidating mechanisms of single-drug escape in a large collection of patient-derived glioma stem cells and tumor specimens; Project 3: Validate in phase III trials a new robust GBM prognostic classifier, the molecular-clinical prognosticator (MCP), and develop clinical diagnostics that predict response to bevacizumab an ipilimumab; Project 4: Modulate GBM induced immunosuppression using a novel p-STAT-3 inhibitor, WP1066. Through this research program and with the full support of The University of Texas M.D. Anderson Cancer Center, this SPORE will make a significant impact toward the diagnosis and treatment of patients with malignant brain tumors.

MD 安德森脑癌 SPORE 更新申请建立在初始资助期间取得的重大进展的基础上，包括新型生物（溶瘤病毒、干细胞）、靶向（PI3K 抑制剂）和免疫调节（p-STAT-3 抑制）的开发治疗策略；以及为 GBM 患者提供个性化护理的生物标志物的开发。在这次更新中，我们的目标是利用这些先前的成功来显着提高恶性胶质瘤患者的生存率。我们建立了一个多学科、综合、灵活和高度转化（从实验室到床边和背部）的研究计划，旨在发现和合理测试新的生物、靶向和免疫疗法，并寻求开发预后和预测生物标志物，为个体化治疗提供信息。 GBM 治疗方法。为了实现我们的目标，我们提出了四个完全转化研究项目（3个治疗性；1个基于人群），所有这些项目都包含基于组织的临床试验，并得到五个核心的支持：管理（A）、病理学和生物样本库（B）、生物统计学和生物信息学 (C)、临床 (D) 和动物 (E)。发展研究计划 (DRP) 和职业发展计划 (CDP) 继续作为我们 SPORE 的成功方面，因为它们鼓励新颖的研究并促进年轻的研究人员。这四个项目的目标是： 项目1：通过将新型溶瘤腺病毒Delta-24-RGD与替莫唑胺结合、利用自噬以及利用骨髓干细胞改善递送来增强其功效； 项目2：通过阐明大量患者来源的胶质瘤干细胞和肿瘤标本中单药逃逸机制，探索基于PISKinase抑制的组合靶向策略； 项目 3：在 III 期试验中验证一种新的稳健的 GBM 预后分类器，即分子临床预测器 (MCP)，并开发预测对贝伐珠单抗和伊匹单抗的反应的临床诊断方法； 项目 4：使用新型 p-STAT-3 抑制剂 WP1066 调节 GBM 诱导的免疫抑制。通过这项研究计划，并在德克萨斯大学MD安德森癌症中心的全力支持下，该SPORE将对恶性脑肿瘤患者的诊断和治疗产生重大影响。