Translational Research in Breast Cancer

乳腺癌的转化研究

• 批准号: 10460204
• 负责人: Xiang Zhang
• 金额: $ 209.15万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10460204
• 关键词: Academia; Advocacy; Advocate; Anatomy; Big Data; Bioinformatics; Biological Assay; Biological Markers; Biology; Biostatistics Core; Breast Cancer Patient; Cancer Biology; Clinical Trials; Clonal Evolution; Collaborations; Common Neoplasm; Data Analyses; Development; Diagnostic; Disease; Eligibility Determination; Ensure; Environment; Equipment; Estrogen receptor positive; Experimental Pathology; Failure; Funding; Future; Genetic Screening; Grant; Human Resources; Immune response; Immunologics; Industry; Informatics; Investigation; Investments; Knowledge; Leadership; Ligands; Medicine; Metastatic breast cancer; Mission; Molecular; Molecular Epidemiology; Monitor; Morbidity - disease rate; Myeloid-derived suppressor cells; NF1 gene; NF1 tumor suppressor; Neoplasm Circulating Cells; Oncogenes; Outcome; PTPN12 gene; Pathologist; Pathology; Pathway interactions; Phase; Phase III Clinical Trials; Phosphotransferases; Population; Precision Medicine Initiative; Protein Kinase; Protocols documentation; Research; Resistance; Resources; Scientist; Stratification; Structure; Techniques; Therapeutic; Translational Research; Treatment Protocols; Tumor Immunity; Tumor Suppressor Genes; Tumor Suppressor Proteins; Tumor-Infiltrating Lymphocytes; advanced breast cancer; biobank; career; clinical translation; college; convict; design; diagnostic tool; drug development; drug repurposing; early phase clinical trial; experience; inhibitor; innovation; malignant breast neoplasm; member; mortality; multidisciplinary; novel therapeutic intervention; novel therapeutics; phase III trial; predictive marker; programs; prospective; proteogenomics; randomized trial; recruit; technological innovation; transcription factor; triple-negative invasive breast carcinoma; tumor; tumor DNA; tumor heterogeneity; tumor immunology

Abstract Lack of progress in curing metastatic breast cancer is due to a number of fundamental treatment barriers. These include insufficient knowledge of therapeutic vulnerabilities, lack of reliable predictive biomarkers, inability to target common tumor suppressor gene loss, inability to target oncogenes that are not protein kinases or ligand- dependent transcription factors, resistance due to clonal evolution and tumor heterogeneity, and failure to mount an immune response against the tumor. This SPORE renewal focuses on these obstacles by articulating cross- cutting objectives and aligned approaches that increase the efficiency of core utilization and promote inter-project collaboration. The three full Projects include studies on how to target the derepressed kinases consequent upon loss of the PTPN12 or the NF1 tumor suppressors in breast cancer, and the development of a promising new therapeutic approach for MYC-positive breast cancer. During the execution of these Projects we will: a) deploy proteogenomic approaches for monitoring kinase targets and resistance pathways; b) establish high-quality biomarkers for clinical trial eligibility and stratification; c) investigate disease-monitoring approaches with circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA); d) incorporate immunological approaches into treatment regimens by increasing the quality and quantity of tumor infiltrating lymphocytes; e) embed our SPORE biomarker program into early phase clinical trials to inform the design of Phase 3 trials; and f) promote collaborative research between Academia, NCI-Supported Cooperative Groups, Industry, and Advocacy Groups. These objectives are served by three reformatted Cores, with the addition of a dedicated and highly-qualified molecular research pathologist for the Pathology and Biobanking Core, the addition of deeper bioinformatics expertise to the Informatics and Biostatistics Core, and a new SPORE director plus additional advocates and advisory board members for the Administration Core. The Career Enhancement and Developmental Research Programs will be guided by highly experienced leadership and, as before, will cement the future of our SPORE. With this powerful enhanced program we will advocate nationally for progress in the treatment of advanced breast cancer, with the conviction that a cure is a near-term possibility.

抽象的 治疗转移性乳腺癌缺乏进展是由于许多基本的治疗障碍。这些 包括对治疗脆弱性认识不足、缺乏可靠的预测生物标志物、无法 针对常见的肿瘤抑制基因丢失，无法针对非蛋白激酶或配体的癌基因 依赖转录因子、克隆进化和肿瘤异质性导致的耐药性以及安装失败 针对肿瘤的免疫反应。 SPORE 更新通过阐述跨领域内容来重点解决这些障碍 削减目标和统一方法，提高核心利用效率并促进项目间合作 合作。这三个完整的项目包括如何针对随后的去抑制激酶的研究 乳腺癌中 PTPN12 或 NF1 肿瘤抑制因子的缺失，以及开发一种有前途的新药物 MYC 阳性乳腺癌的治疗方法。在这些项目的执行过程中，我们将：a) 部署 用于监测激酶靶点和耐药途径的蛋白质组学方法； b) 建立高质量 用于临床试验资格和分层的生物标志物； c) 研究疾病监测方法 循环肿瘤细胞（CTC）和循环肿瘤DNA（ctDNA）； d) 结合免疫学方法 通过增加肿瘤浸润淋巴细胞的质量和数量来纳入治疗方案； e) 嵌入我们的 SPORE 生物标志物计划进入早期临床试验，为 3 期试验的设计提供信息； f) 促进 学术界、NCI 支持的合作团体、工业界和倡导者之间的合作研究 团体。 这些目标由三个重新调整的核心来实现，并增加了一个敬业且高素质的核心 病理学和生物样本库核心的分子研究病理学家，增加了更深入的生物信息学 信息学和生物统计学核心的专业知识，以及新的 SPORE 主任以及其他倡导者和 行政核心顾问委员会成员。职业提升和发展研究 这些计划将由经验丰富的领导层指导，并将一如既往地巩固我们 SPORE 的未来。 通过这一强有力的增强计划，我们将在全国范围内倡导晚期晚期患者治疗方面的进展 乳腺癌，相信近期有可能治愈。