Targeting Epigenomics in Myeloid Neoplasms

髓系肿瘤的表观基因组靶向

• 批准号: 7092257
• 负责人: STEVEN D GORE
• 金额: $ 14.2万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-08 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7092257
• 关键词: acute myelogenous leukemia; azacitidine; chromatin immunoprecipitation; clinical research; clinical trial phase I; clinical trial phase II; combination chemotherapy; drug screening /evaluation; gene expression; gene targeting; high performance liquid chromatography; human subject; human therapy evaluation; mass spectrometry; neoplasm /cancer chemotherapy; patient oriented research; phenylamide; polymerase chain reaction; therapy design /development

DESCRIPTION (provided by applicant): Drug development in the era of biologically rational, "targeted therapeutics" in oncology requires specific expertise and complex skill sets. Far from previous paradigms in which drugs were plugged in to standard dose escalation schemata with dose limiting toxicity as the primary endpoint, today's investigators must develop creative trial designs which are appropriate for the specific agent and its specific targeted use. The investigator must be able to speak to the laboratory scientist working out the basic biological concepts, the pharmaceutical company which provides the drug, the analytic pharmacologists, biostatisticians, internal review boards and government regulators. Most importantly, the drug developer must be able to organize and lead a team effort, marshalling the resources at hand to design and execute a trial which is feasible, cost-effective, biologically and clinically sound, and which helps determine clinical and biological efficacy. The investigator must be able to glean information from the trial with which he or she can go back to the laboratory investigator and inform the basic investigation, forming an iterative process of discovery from bench to bedside to bench. Having acquired considerable unique expertise in the development of biologically driven therapies in myeloid malignancies, I am eager to spend more time mentoring developing investigators, transmitting my experience to a new generation. In the mentoring relationship, both mentor and trainee learn from each other and grow together. The Sidney Kimmel Comprehensive Cancer Center is a unique institution which provides outstanding resources for drug development in an academic center. I have organized a dynamic program focused on the translation of cutting edge basic science concerning the epigenetic regulation of gene expression to the rational non-cytotoxic treatment of myeloid malignancies. This program provides an outstanding venue for the training of young investigators; this K24 award will provide me with protected time to devote to that important endeavor and to further the accomplishment of my mission to develop effective therapies for this difficult group of patients.

描述（由申请人提供）：在生物学合理的时代，肿瘤学“靶向治疗”的药物开发需要特定的专业知识和复杂的技能。与以前将药物插​​入标准剂量递增方案并以剂量限制毒性作为主要终点的范例不同，今天的研究人员必须开发适合特定药物及其特定目标用途的创造性试验设计。研究者必须能够与研究基本生物学概念的实验室科学家、提供药物的制药公司、分析药理学家、生物统计学家、内部审查委员会和政府监管机构进行交流。最重要的是，药物开发商必须能够组织和领导团队合作，整合手头的资源来设计和执行可行的、具有成本效益的、生物学和临床上合理的试验，并有助于确定临床和生物学功效。研究者必须能够从试验中收集信息，然后他或她可以返回实验室研究者并为基本调查提供信息，形成从实验室到床边再到实验室的迭代发现过程。在开发髓系恶性肿瘤的生物驱动疗法方面获得了相当多的独特专业知识，我渴望花更多时间指导开发研究人员，将我的经验传授给新一代。在师徒关系中，师徒双方互相学习、共同成长。悉尼金梅尔综合癌症中心是一个独特的机构，为学术中心的药物开发提供优秀的资源。我组织了一个充满活力的项目，重点是将有关基因表达的表观遗传调控的前沿基础科学转化为骨髓恶性肿瘤的合理非细胞毒性治疗。该项目为年轻研究者的培训提供了良好的场所；这个 K24 奖项将为我提供受保护的时间来致力于这一重要的努力，并进一步完成我为这一困难患者群体开发有效疗法的使命。