The Development of Novel Individualized Therapy for Triple-Negative Breast Cancer

三阴性乳腺癌新型个体化疗法的开发

• 批准号: 8581422
• 负责人: Jennifer R Diamond
• 金额: $ 17.17万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581422
• 关键词: Accounting; Antineoplastic Agents; Area; Bioinformatics; Biological; Biological Markers; Biopsy; Breast; Breast Cancer Cell; CCR; Cancer Patient; Cell Line; Cell division; Cessation of life; Characteristics; Clinical; Clinical Drug Development; Clinical Research; Clinical Trials; Clinical Trials Design; Colorado; DNA Repair Pathway; DNA Sequence; Data; Development; Development Plans; Developmental Therapeutics Program; Diagnosis; Diamond; Disease; Distant Metastasis; Doctor of Philosophy; Drug Kinetics; Enrollment; Ensure; Family; Frequencies; Functional disorder; Funding; Future; Gene Mutation; Genes; Genomics; Goals; Grant; Human; Individual; Institution; Interdisciplinary Study; Investigation; K-Series Research Career Programs; Laboratories; Lead; Mammary Neoplasms; Medical Oncology; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Mitotic; Modeling; Newly Diagnosed; Nuclear Grade; Outcome; Pathway interactions; Patient Selection; Patients; Pharmaceutical Preparations; Phase II Clinical Trials; Phenotype; Phosphotransferases; Pre-Clinical Model; Predictive Value; Primary Neoplasm; Protein-Serine-Threonine Kinases; Publications; Publishing; Research; Research Personnel; Research Training; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; Scientist; Signal Transduction; Site; Staging; THBS1 gene; Testing; Time; Tissue Sample; Tissues; Toxic effect; Training; Translating; Translational Research; Tumor Tissue; Tumor-Derived; United States National Institutes of Health; Universities; Virginia; Work; Xenograft Model; Xenograft procedure; animal model development; anticancer research; arm; aurora kinase; aurora-A kinase; base; biobank; cancer care; cancer cell; career; career development; clinical efficacy; design; drug development; effective therapy; human STK6 protein; improved; inhibitor/antagonist; kinase inhibitor; malignant breast neoplasm; mutant; novel; oncology; patient oriented; patient population; phase 1 study; population based; pre-clinical; prevent; professor; programs; public health relevance; response; responsible research conduct; small molecule; success; tool; transcriptome sequencing; translational clinical trial; triple-negative invasive breast carcinoma; tumor

DESCRIPTION (provided by applicant): Jennifer R. Diamond, MD is a clinician-scientist with strong training in translational breast cancer research with a strong commitment to developing new therapies for the treatment of triple-negative breast cancer. Dr. Diamond is an Assistant Professor of Medicine in the Division of Medical Oncology at the University of Colorado Denver (CU), where she serves as a bridge between the Breast Oncology and Developmental Therapeutics programs. Her long-term career goal is to lead a multidisciplinary research team in translating preclinical biomarker discovery into more effective "personalized" medicine for patients with breast cancer. The candidate will develop expertise in translational clinical trial design and implementation, successful acquisition and interpretation of correlative tissue studies, and advanced topics in bioinformatics through this K23 Mentored Patient-Oriented Career Development Award. The candidate's short-term career goal is to establish herself as an independent investigator in developmental therapeutics and breast oncology with the preliminary data, research training, and publication record necessary to be competitive for NIH project grant funding. The K23 Mentored Patient-Oriented Research Career Development Award with help her to achieve these goals by: 1) granting her protected time to develop a clinical and translational research career under the guidance of a team of mentors dedicated to her success, 2) allowing her to receive specialized training in the design of biomarker-driven clinical trials, bioinformatics, and the responsible conduct of research through direct interaction with mentoring scientists and supplemental didactics, and 3) providing her the opportunity to gain recognition as a researcher in the field of drug development and breast oncology. The candidate's research plan aims to complete a single-arm, dual institution, two-stage phase II clinical trial of ENMD-2076 in patients with advanced or metastatic, previously treated TNBC that was conceived and designed by Dr. Diamond. This clinical trial is open to accrual as of July 2012 and funded by the NIH (1R21CA164617-01A1, PI Diamond). A secondary aim of this study is to explore genomic biomarkers predictive of clinical response to ENMD-2076 in this patient population based on unique preclinical data generated in Dr. Diamond's laboratory investigating p53-based genomic classifiers. The overall goal of this proposal is to develop novel and effective therapy for advanced TNBC, including the investigation of unique biomarker selection strategies which represents a major area of unmet need in human cancer care. Dr. Diamond has assembled a mentorship team of independently- funded, internationally-recognized investigators with expertise in breast cancer clinical trials and correlative tissue testing (Virginia Borges, MD), translational clinical trials, preclinical biomarker development and animal modeling (S. Gail Eckhardt, MD, Dan Gustafson, PhD), bioinformatics (Aik Choon Tan, PhD) and p53 signal transduction in cancer cells (Joaquin Espinosa, PhD). In conjunction with her mentorship team, the candidate has developed a detailed career development plan which will ensure that she successfully transitions to a leader in new drug development in breast cancer, capable of advancing the field and improving outcomes for patients with advanced triple-negative breast cancer.

简介（由申请人提供）：Jennifer R. Diamond博士是一名临床医生兼科学家，在转化乳腺癌研究方面受过良好的培训，致力于开发治疗三阴性乳腺癌的新疗法。戴蒙德博士是科罗拉多大学丹佛分校（CU）肿瘤科医学助理教授，在那里她是乳腺肿瘤学和发育治疗学项目之间的桥梁。她的长期职业目标是领导一个多学科研究团队，将临床前生物标志物发现转化为更有效的“个性化”乳腺癌患者药物。候选人将通过K23指导患者导向职业发展奖，在转化临床试验的设计和实施、相关组织研究的成功获取和解释以及生物信息学的高级主题方面发展专业知识。候选人的短期职业目标是使自己成为发育治疗学和乳腺肿瘤学领域的独立研究者，拥有必要的初步数据、研究培训和发表记录，以竞争NIH项目资助。K23指导患者导向研究职业发展奖帮助她实现了这些目标：1)在一组致力于她成功的导师的指导下，给予她保护时间发展临床和转化研究事业；2)让她接受生物标志物驱动临床试验设计、生物信息学和通过直接互动负责任的研究行为方面的专业培训