SPORE in Brain Cancer

脑癌中的孢子

• 批准号: 8548737
• 负责人: FREDERICK F LANG
• 金额: $ 204.23万
• 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/8548737
• 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 Anderson脑癌孢子的更新应用是建立在初始资金期间取得的重大进展的基础上的，包括开发新型生物学（溶瘤病毒，干细胞），靶向（PI3K抑制剂）和免疫统治（P-STAT-3抑制作用）治疗策略；以及开发生物标志物，为GBM患者提供个性化护理。在这种续约中，我们的目标是利用这些先前的成功，以显着改善恶性神经胶质瘤患者的生存。我们已经建立了一个多学科，综合，灵活的，高度转化的（床头和背部）研究计划，旨在发现和合理地测试新的生物学，有针对性和免疫学疗法，并旨在开发预后和预测性的生物标志物，从而为GBM治疗提供个性化方法。为了实现我们的目标，我们提出了四个完全转化的研究项目（3个治疗性； 1个基于人群的），所有这些项目均包含基于组织的临床试验，并得到了五个核心的支持：行政（A），病理学和生物疗法（B），生物统计学和生物信息学和生物信息信息学（C），临床（D）和动物（E）。发展研究计划（DRP）和职业发展计划（CDP）继续作为我们孢子的成功方面，因为它们鼓励新颖的研究并促进年轻的研究人员。这四个项目的目的是： 项目1：通过利用自噬和使用骨髓干细胞改善递送，通过将其与替莫唑胺结合结合，增强了新型肿瘤腺病毒Delta-24-RGD的疗效； 项目2：通过在大量患者衍生的神经胶质瘤干细胞和肿瘤标本中阐明单药逃脱的机制，探索基于Piskinase抑制的组合靶向策略； 项目3：在第三阶段试验中验证了一种新的强大GBM预后分类器，分子 - 临床预后剂（MCP），并开发临床诊断，以预测对贝伐单抗的反应； 项目4：使用新型的P-STAT-3抑制剂WP1066调节GBM诱导的免疫抑制。通过该研究计划，并在德克萨斯大学医学博士Anderson癌症中心的全部支持下，该孢子将对诊断和治疗恶性脑肿瘤患者产生重大影响。