Clinical and Molecular Studies of Novel Therapeutics in Malignant Brain Tumors

描述（由申请人提供）：本提案，“恶性脑肿瘤新疗法的临床和分子研究”，建立在我在马萨诸塞州总医院进行富有成效的、以患者为导向的神经肿瘤学研究并担任9名学员的主要导师的经验基础上。该奖项的重点是为胶质母细胞瘤患者开发更好的治疗方法，胶质母细胞瘤是一种致命的癌症。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药物的新临床试验。这些研究将建立在现有的，资助的，2期试验的目标是针对胶质母细胞瘤的多个分子途径。该申请中提出的新研究靶向PI 3 K/Akt/mTOR细胞信号通路和VEGF介导的血管生成级联反应，以改善胶质母细胞瘤患者的预后。我已经能够建立一个优秀的研究环境中进行这些研究。资源包括一个全面的，纵向的，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;一个资金充足，富有成效的高级合作者的杰出团队;一个大型脑肿瘤患者群体;一个不断扩大的人才库和一个机构的K12培训补助金在神经肿瘤学。通过更好地协调临床研究计划;更多的时间来开发具有新终点的新研究，更多的时间来指导神经肿瘤学学员，该奖项将提高我作为临床研究者的职业生涯，扩大我的资助支持，并使我能够培养实习毕业生，他们准备在以患者为导向的神经肿瘤学研究中获得自己的资助支持。

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.