Targeting Epigenomics in Myeloid Neoplasms

髓系肿瘤的表观基因组靶向

基本信息

批准号：
7649402
负责人：
STEVEN D GORE
金额：
$ 15.02万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
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/7649402
关键词：
Accounting Acute Myelocytic Leukemia Azacitidine Back Basic Science Benzamides Bioavailable Biological Biological Availability Cells Clinical Clinical Trials Clinical Trials Design Complex Comprehensive Cancer Center CpG Islands DMA-methyltransferase DNA DNA Damage DNA Modification Methylases Data Development Disease Dose Dose-Limiting Drug Kinetics Dysmyelopoietic Syndromes Epigenetic Process Gene Expression Regulation Gene Silencing Generations Genes Glean Government Half-Life Hand Histone Acetylation Histone Deacetylase Histone Deacetylase Inhibitor Histones Hour In Vitro Institution Intravenous infusion procedures Investigation Laboratories Laboratory Scientists Laboratory Study Lead Learning Link MS-275 Marshal Mentors Methylation Mid-Career Clinical Scientist Award (K24)Mission Myeloproliferative disease Nucleosides Oral Patients Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Phase II Clinical Trials Phenotype Phenylbutyrates Play Plug-in Process Promoter Regions Proteins Randomized Controlled Clinical Trials Reagent Recruitment Activity Regulator Genes Relapse Research Personnel Resources Role Schedule Serum Sodium phenylbutyrate Testing Time Toxic effect Training Translations Vorinostat Work ataxia telangiectasia mutated protein bench to bedside cancer cell chromatin remodeling cost cytotoxic density design drug development effective therapy epigenomics experience gene repression high risk inhibitor/antagonist nano novel oncology programs promoter response skills sound therapeutic target

项目摘要

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）：在生物学上合理的“靶向治疗剂”中的药物开发需要特定的专业知识和复杂的技能。当今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，远非以前将药物插入标准剂量升级方案中的范式，而剂量限制了毒性。研究人员必须能够与实验室科学家交谈，以提供基本生物学概念，该公司提供药物，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。最重要的是，药物开发人员必须能够组织和领导团队的努力，编组手头的资源，以设计和执行可行，具有成本效益，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。研究人员必须能够从他或她可以回到实验室调查员的试验中收集信息，并为基本调查提供通知，从而构成了从长凳到床边再到长凳的迭代发现过程。在获得髓样恶性肿瘤中生物学驱动疗法的开发方面获得了相当大的独特专业知识，我渴望花更多的时间指导开发研究人员，将我的经验传递给新一代。在指导关系中，导师和受训者都互相学习并共同成长。 Sidney Kimmel综合癌症中心是一个独特的机构，为学术中心提供了出色的药物开发资源。我已经组织了一个动态计划，重点是尖端基础科学的翻译，该计划涉及基因表达的表观遗传调节，以对髓样恶性肿瘤的合理非毒性治疗进行表观遗传调节。该计划为培训年轻调查人员提供了一个杰出的场所；这项K24奖将为我提供受保护的时间，以致力于这项重要的努力，并进一步完成我为这群困难的患者开发有效疗法的使命。