Clinical and Molecular Studies of Novel Therapeutics in Malignant Brain Tumors

描述(申请人提供)：这项名为“恶性脑瘤新疗法的临床和分子研究”的提案，基于我在过去9年中在马萨诸塞州总医院进行富有成效的、以患者为中心的神经肿瘤学研究的经验，并担任9名学员的主要导师。该奖项的重点是为胶质母细胞瘤患者开发改进的治疗方法，胶质母细胞瘤是一种普遍致命的癌症。该奖项将使我能够获得受保护的时间和资源进行研究和指导，并将使我能够扩大我的NIH资助的研究计划，以开发具有新的分子和成像终点的分子靶向制剂的新临床试验。这些研究将建立在现有的、有资金支持的2期试验的基础上，目标是针对胶质母细胞瘤的多个分子途径。申请中提出的新研究针对PI3K/Akt/mTOR细胞信号通路和VEGFR介导的血管生成级联反应，以努力改善胶质母细胞瘤患者的预后。我已经能够建立一个出色的研究环境来进行这些研究。资源包括一个全面的、纵向的、经IRB批准的与脑肿瘤组织库链接的患者研究数据库；来自NCI和行业的新型药物管道；临床试验/研究的广泛支持基础设施；一群资金雄厚、富有成效的资深合作者的杰出团队；大量脑瘤患者；不断扩大的有才华的研究人员库和神经肿瘤学K12机构培训补助金。通过更好地协调临床研究计划；更多时间开发具有新终点的新研究，以及更多时间指导神经肿瘤学实习生该奖项将加强我作为临床研究员的职业生涯，扩大我的补助金支持，并使我能够培养出准备获得自己的补助金支持的实习生毕业生，以患者为导向的神经肿瘤学研究的生产性职业。

DESCRIPTION (provided by applicant): This proposal, "Clinical and molecular studies of novel therapeutics in malignant brain tumors", builds upon my experience conducting productive, patient-oriented, neuro-oncology research and serving as the primary mentor for 9 trainees over the past 9 years at the Massachusetts General Hospital. The focus of this award is to develop improved treatment for patients with glioblastoma, a uniformly fatal cancer. The award would enable me to secure protected time and resources for research and mentoring and would enable me to expand my NIH-funded research program to develop new clinical trials of molecularly-targeted agents with novel molecular and imaging endpoints. These studies would build upon existing, funded, phase 2 trials with the goal of targeting multiple molecular pathways in glioblastoma. New research proposed in the application targets the PI3K/Akt/mTOR cell signaling pathway and the VEGFR-mediated angiogenesis cascade in an effort to improve outcome in glioblastoma patients. I have been able to establish an outstanding research environment in which to conduct these studies. Resources include a comprehensive, longitudinal, electronic IRB-approved, patient research database linked to a brain tumor tissue bank; a pipeline of novel agents from the NCI and industry; an extensive support infrastructure for clinical trials/research; an outstanding group of well-funded, productive, senior collaborators; a large brain tumor patient population; an expanding pool of talented research fellows and an institutional K12 training grant in neuro-oncology. Through better coordination of the clinical research program; more time to develop new studies with novel endpoints and more time to mentor neuro-oncology trainees this award will enhance my career as a clinical investigator, expand my grant support and enable me to produce trainee graduates who are poised to secure their own grant support for productive careers in patient-oriented neuro-oncology research.