Mayo Clinic Breast Cancer SPORE

梅奥诊所乳腺癌孢子

基本信息

批准号：
9340070
负责人：
MATTHEW Philip GOETZ
金额：
$ 243.85万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-22 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9340070
关键词：
ATM gene Address Adjuvant Affect Agonist Androgen Receptor Area Aromatase Inhibitors BARD1 gene BRCA1 gene BRCA2 gene Bioinformatics Biological Assay Biometry Breast Breast Cancer therapy CDH1 gene CHEK2 gene Clinic Clinical Clinical Management Clinical Research Clinical Trials Collaborations Cystatins Data Development Disease Disease Resistance Drug Targeting Endocrine Estradiol Estrogen Receptor alpha Estrogen Receptor beta Estrogens Exhibits Family history of Funding Future Generic Drugs Genes Genetic Variation Genome Goals Growth Guidelines Human Immunotherapy Individual Leadership Ligands MSH6 gene Malignant Neoplasms Mayo Clinic Cancer Center Measles Measles virus Metastatic breast cancer Mission Morbidity - disease rate Mutation Oncolytic Organ Pathogenicity Pathologic Pathology Pathway interactions Penetrance Performance Pharmaceutical Preparations Pharmacogenomics Phenotype Positioning Attribute Postmenopause Program Development Protein Family RAD51C gene Recommendation Regimen Registries Reproduction spores Research Research Personnel Research Project Grants Resistance Risk Risk Assessment Risk Estimate Risk Reduction Safety Science Scientist Signal Transduction Susceptibility Gene Testing Transforming Growth Factor beta Transgenes Translating Translational Research United States National Institutes of Health Validation Variant Viral Vision Woman Work age related anticancer research antitumor effect base cancer recurrence cancer risk career career development chemotherapy clinically relevant design faculty support genetic panel test genetic variant genome-wide analysis immune checkpoint immunogenic immunogenicity improved innovation instrument malignant breast neoplasm mortality new therapeutic target novel patient registry phase 1 study phase 2 study phase II trial pre-clinical prognostic programs prospective receptor expression response secondary analysis symposium therapeutic target translational cancer research translational research program triple-negative invasive breast carcinoma tumor tumor growth uptake variant of unknown significance

项目摘要

Program Summary/Abstract This second renewal application of the Mayo Clinic Breast Cancer SPORE is being submitted with the vision that the burden of breast cancer can be reduced through the performance of innovative translational research addressing issues of high significance for women. The science of the SPORE includes four translational research projects. Project 1: “Cancer risks for mutations in breast cancer predisposition genes” focuses on non-BRCA1/BRCA2 genes included in “panel based” tests. Using the PROMPT registry, the investigators will define the penetrance of breast cancers associated with inactivating mutations, the clinical relevance of variants of uncertain significance, and pathological “phenotype” of these mutations. Project 2: “Therapeutic targeting of ERβ in triple negative breast cancer (TNBC)” is based on Mayo investigator data that ERβ, when expressed in TNBC, is prognostic, and that ERβ agonists suppress proliferation through the TGFβ pathway. This project culminates in a phase II study of estradiol in ERβ+TNBC within the Translational Breast Cancer Research Symposium. Project 3: “Measles virus based immunovirotherapy in the treatment of metastatic breast cancer” is based on pioneering work of Mayo investigators to develop a measles virus (MV) that expresses an immunostimulatory transgene (MV-NAP), and the synergistic antitumor activity of MV-NAP with PD-1 blockade. This project includes a MV-NAP phase I study, and development of additional preclinical data that will inform the clinical trial of the combination of MV-NAP and PD-1 blockade. Project 4: “Pharmacogenomics of aromatase inhibitors (AI) in early stage postmenopausal breast cancer” is based upon the importance of estrogen levels in AI-treated women. The investigators plan secondary analyses of adjuvant AI trials to determine whether inadequate estrogen suppression is associated with cancer recurrence, followed by a genome-wide analysis to identify genetic variants associated with the “optimal” estrogen threshold and then prospective validation in a clinical study. These research projects are supported by three highly interactive cores: Core A: Administrative Core, Core B: Biospecimen and Pathology Core, and Core C: Biostatistics, Bioinformatics, and Patient Registry Core. A Developmental Research Program will continue to identify and develop research projects that hold the greatest promise to advance to full SPORE projects, and a Career Enhancement Program will continue to identify and support faculty investigators in breast cancer translational research that have the greatest potential to become future SPORE leaders. The investigators, cores, and the research programs in the SPORE are all integrated in the Mayo Clinic Cancer Center. Collectively, our SPORE will make discoveries and translate them into the clinic for the benefit of women with, or at risk of breast cancer.

程序摘要/摘要蛋黄酱诊所乳腺癌孢子的第二次续签应用正在与视力一起提交通过创新转化研究的表现，可以减少乳腺癌的灼伤解决对妇女具有很高意义的问题。孢子的科学包括四个翻译研究项目。项目1：“乳腺癌突变的癌症风险易感基因”的重点非BRCA1/BRCA2基因包含在“基于面板”的测试中。使用及时注册表，调查人员将定义与灭活突变相关的乳腺癌的外观，这些突变的不确定意义的变体和病理“表型”。项目2：“治疗性 ERβ在三重阴性乳腺癌（TNBC）中的靶向”是基于Mayo研究者的数据，即ERβ，当在TNBC中表达的是预后，ERβ激动剂通过TGFβ途径抑制增殖。该项目最终在翻译乳腺癌中ERβ+TNBC中的雌二醇II期研究中达到顶点研究研讨会。项目3：“在转移性治疗中，基于麻疹病毒的免疫疗法乳腺癌”是基于梅奥研究人员开发出麻疹病毒（MV）的开创性工作免疫刺激转化（MV-NAP），以及MV-NAP与PD-1阻滞的协同抗肿瘤活性。该项目包括MV-NAP I阶段研究，并开发其他临床前数据，这些数据将告知 MV-NAP和PD-1封锁的组合的临床试验。项目4：“药物基因组学绝经后乳腺癌的早期芳香酶抑制剂（AI）基于 AI治疗的女性的雌激素水平。调查人员计划调整AI试验的次要分析确定雌激素抑制不足是否与癌症复发有关，其次是全基因组分析以确定与“最佳”雌激素阈值相关的遗传变异临床研究中的前瞻性验证。这些研究项目得到了三个高度互动的支持核心：核心A：行政核心，核心B：生物渗透和病理核心以及核心C：生物统计学，，生物信息学和患者注册表核心。发展研究计划将继续识别和开发研究项目，该项目具有最大的前景，可以晋升为全孢子项目，并且职业生涯增强计划将继续识别和支持乳腺癌翻译中的教师调查员具有成为未来孢子领导者的最大潜力的研究。调查人员，核心和孢子中的研究计划都集成在梅奥临床癌症中心。总体而言，我们的孢子将发现发现并将其转化为诊所癌症。