Investigating Resistance to FLT3 Inhibitors in AML

研究 AML 对 FLT3 抑制剂的耐药性

• 批准号: 8749807
• 负责人: Catherine Choy Smith
• 金额: $ 17.58万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8749807
• 关键词: Acute Myelocytic Leukemia; Address; Affect; Affinity; American; Architecture; Back; Binding; Biochemical; Biochemistry; Biological; Cell model; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials; Clonal Evolution; Collection; Combined Modality Therapy; Community Physician; Data; Development; Disease; Disease Resistance; Disease remission; Drug Interactions; Drug resistance; Education; Enrollment; Environment; Funding; Future; Genes; Genetic; Genetic Determinism; Genomics; Goals; Health; Heterogeneity; Human; Individual; Institution; Knowledge; Laboratory Research; Lead; Malignant Neoplasms; Mediating; Mentors; Molecular; Mutate; Mutation; Oncogenic; Outcome; Patients; Phosphotransferases; Principal Investigator; Proteins; Proteomics; Publishing; Relapse; Research; Research Personnel; Resistance; Resources; Sampling; Scientist; Signal Transduction; Specimen; Technology; Testing; Therapeutic; Time; Training; Translating; Translations; Tyrosine Kinase Inhibitor; Vascular Endothelial Growth Factor Receptor-1; Work; bench to bedside; career development; clinically relevant; cohort; drug sensitivity; experience; fitness; genome-wide analysis; improved; inhibitor/antagonist; insight; leukemia; next generation; next generation sequencing; novel therapeutics; outcome forecast; patient population; pressure; protein function; protein structure; resistance mechanism; resistance mutation; response

DESCRIPTION (provided by applicant): The broad goal of the proposed application is train Dr. Smith, a candidate with demonstrated potential as a clinical-translational researcher in leukemia into an independent principal investigator capable of effectively mediating the "bedside to bench and back" translation of genomic data into functional studies that will facilitate the development of clinically effective therapeutics for acute myeloid leukemia. The research plan incorporates the proposed training goals of education and experience in the use of 1) emerging genomic technologies, particularly analysis of next-generation sequencing data, 2) biochemistry and proteomics, with an emphasis on the study of kinase function and 3) cellular models of oncogenic signaling and transformation through the scientific aims of 1) defining and validating genetic changes associated with resistance to clinically active investigational FLT3 inhibitors and 2) defining the molecular impact of quizartinib-resistant FLT3 kinase domain mutations. The application incorporates a combination of coursework, tutorials, mentoring and direct laboratory research experience set in the unparalleled scientific environment of UCSF, a world-renowned research institution with a well-established NCI-funded Comprehensive Cancer, multiple institutional resources and a distinguished community of physician-scientists.

描述（由申请人提供）：拟议申请的广泛目标是将Smith博士（一名具有白血病临床转化研究潜力的候选人）培养为独立的主要研究者，能够有效地将基因组数据的“床边到后台”转化为功能研究，从而促进急性髓性白血病临床有效治疗方法的开发。该研究计划纳入了拟议的教育和经验的培训目标，在使用1）新兴的基因组技术，特别是下一代测序数据的分析，2）生物化学和蛋白质组学，重点是激酶功能的研究和3）致癌信号传导和转化的细胞模型，通过以下科学目的：1）定义和验证与临床活性研究性FLT3抑制剂耐药相关的遗传变化，以及2）定义喹扎替尼耐药FLT3激酶结构域突变的分子影响。该应用程序结合了课程，教程，指导和直接实验室研究经验，在UCSF无与伦比的科学环境中设置，UCSF是一个世界知名的研究机构，拥有完善的NCI资助的综合癌症，多个机构资源和杰出的医生科学家社区。