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: 8927557
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8927557
• 关键词: Accounting; Antineoplastic Agents; Area; Bioinformatics; Biological; Biological Markers; Biopsy; Breast; Breast Cancer Cell; Breast Cancer Patient; CCR; 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; DNA Sequence Alteration; 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; Genes; Genomics; Goals; Grant; Health; 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; personalized medicine; phase 1 study; population based; pre-clinical; prevent; professor; programs; response; responsible research conduct; small molecule; success; targeted treatment; 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.

描述（由申请人提供）：Jennifer R. Diamond，MD是一位临床科学家，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。Diamond博士是科罗拉多丹佛大学（CU）医学肿瘤学系的医学助理教授，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”药物，用于乳腺癌患者。候选人将通过这个K23指导的以患者为导向的职业发展奖，发展翻译临床试验设计和实施，成功获取和解释相关组织研究以及生物信息学高级主题的专业知识。候选人的短期职业目标是建立自己作为一个独立的研究者在发育治疗学和乳腺肿瘤学的初步数据，研究培训和出版记录，必要的NIH项目资助的竞争力。K23指导的以患者为导向的研究职业发展奖通过以下方式帮助她实现这些目标：1）在致力于她成功的导师团队的指导下，给予她受保护的时间来发展临床和转化研究职业生涯，2）允许她接受生物标志物驱动的临床试验设计，生物信息学和通过直接互动负责任地进行研究的专业培训 与指导科学家和补充教学法，和3）为她提供机会，以获得承认，作为一个研究人员在药物开发和乳腺肿瘤学领域。候选人的研究计划旨在完成由Diamond博士构思和设计的ENMD-2076在晚期或转移性既往治疗过的TNBC患者中的单臂，双机构，两阶段II期临床试验。本临床试验自2012年7月起开始招募，由NIH资助（1 R21 CA 164617 - 01 A1，PI Diamond）。本研究的第二个目的是基于Diamond博士实验室研究基于p53的基因组分类器产生的独特临床前数据，探索预测该患者人群对ENMD-2076临床应答的基因组生物标志物。该提案的总体目标是为晚期TNBC开发新的有效疗法，包括研究独特的生物标志物选择策略，这是人类癌症护理中未满足需求的主要领域。Diamond博士组建了一个由独立资助、国际公认的研究人员组成的导师团队，他们在乳腺癌临床试验和相关组织检测（Virginia Borges，MD）、转化临床试验、临床前生物标志物开发和 动物模型（S. Gail Eckhardt，MD，Dan Gustafson，PhD）、生物信息学（Aik Choon Tan，PhD）和癌细胞中的p53信号转导（Joaquin埃斯皮诺萨，PhD）。与她的导师团队一起，候选人制定了详细的职业发展计划，这将确保她成功过渡到乳腺癌新药开发的领导者，能够推进该领域并改善晚期三阴性乳腺癌患者的预后。