Targeting Epigenomics in Myeloid Neoplasms

描述（由申请人提供）：生物理性时代的药物开发，肿瘤学的“靶向治疗”需要特定的专业知识和复杂的技能。与以往将药物纳入标准剂量递增模式，以剂量限制毒性为主要终点的模式不同，今天的研究人员必须开发出适合特定药物及其特定靶向使用的创造性试验设计。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谈。最重要的是，药物开发人员必须能够组织和领导一个团队，整理手头的资源，设计和执行一个可行的、具有成本效益的、生物学和临床合理的试验，并有助于确定临床和生物学疗效。调查员必须能够从试验中收集信息，这样他或她就可以回到实验室调查员那里，为基础调查提供信息，形成一个从工作台到床边再到工作台的反复发现过程。在髓系恶性肿瘤生物驱动疗法的开发方面获得了相当多的独特专业知识，我渴望花更多的时间指导发展中的研究人员，将我的经验传授给新一代。在师徒关系中，导师和学员相互学习，共同成长。Sidney Kimmel综合癌症中心是一个独特的机构，它为药物开发提供了优秀的学术中心资源。我组织了一个动态项目，专注于将有关基因表达的表观遗传调控的前沿基础科学转化为髓系恶性肿瘤的合理非细胞毒性治疗。该项目为培养年轻研究人员提供了一个绝佳的场所；这个K24奖项将为我提供有保障的时间来致力于这项重要的努力，并进一步完成我的使命，为这一困难的患者群体开发有效的治疗方法。

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.