权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

06 Breast Cancer

06 乳腺癌

基本信息

批准号：
10467001
负责人：
KELLY K HUNT
金额：
$ 1.87万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-08-28 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10467001
关键词：
Address American Joint Committee on Cancer Area Basic Science Biological Assay Biological Factors Biology Breast Breast Cancer Patient Breast Cancer Treatment Breast cancer metastasis CCNE1 gene Cancer Center Support Grant Catchment Area Cell Cycle Cells Clinical Clinical Investigator Clinical Research Clinical Trials Collaborations Communication DNA Repair Development Diagnosis Disease ERBB2 gene Early Diagnosis Epithelial Evolution FRAP1 gene Faculty Funding Generations Genetically Engineered Mouse Genets Genomics Goals Grant Incidence Individual Journals Knowledge Laboratories Link Long-Term Effects Longevity Malignant Neoplasms Mammary Neoplasms Maps Measures Mediator of activation protein Medical Oncologist Mesenchymal Metastatic Neoplasm to the Bone Methods MicroRNAs Minor Modeling Molecular Morbidity - disease rate Mutation Nature Neoplasm Metastasis Paper Pathway interactions Patients Peer Review Phenotype Philanthropic Fund Population Population Research Population Study Prevention Primary Neoplasm Prognosis Publishing Publishing Peer Reviews Research Research Infrastructure Research Personnel Resistance Resource Sharing Signal Transduction Staging System Subgroup Surgical Oncologist System TP53 gene Techniques Technology Texas Therapeutic Translating Translational Research Tumor stage United States Wages Woman advanced disease anticancer research base biomarker-driven burden of illness clinical practice cohort data registry early detection biomarkers effective therapy fundamental research improved innovation interest malignant breast neoplasm member molecular marker mortality neoplasm registry neoplastic cell novel therapeutic intervention novel therapeutics overexpression personalized medicine pre-clinical predicting response prognosis biomarker prognostic programs recruit response biomarker single cell sequencing targeted treatment therapeutic target treatment effect treatment response treatment strategy trend triple-negative invasive breast carcinoma tumor growth tumor heterogeneity tumor initiation tumor progression tumorigenesis vector

项目摘要

PROJECT SUMMARY/ABSTRACT The Breast Cancer Program (BrCP) consists of 72 members (60 primary, 12 associate) from 25 departments. The program is led by Dr. Kelly K. Hunt, breast surgical oncologist and clinical investigator; Dr. Khandan Keyomarsi, laboratory-based investigator; and Dr. Debu Tripathy, breast medical oncologist and clinical investigator. The major scientific goal of the BrCP is to elucidate mechanisms of cancer evolution and metastasis that can be translated into new treatment strategies for breast cancer patients. There are 3 themes: 1) Genetic Alterations and Breast Cancer Evolution, 2) Biology of Established Breast Cancer, and 3) Targeted Therapy in Breast Cancer. They have led to 3 specific aims: Aim 1: to elucidate the molecular and genomic evolutionary basis of breast cancer development and progression; Aim 2: to examine the deregulation of signal transduction, DNA repair, cell-cycle, and differentiation pathways in breast cancer that could provide therapeutic targets; Aim 3: to leverage scientific discoveries into novel therapeutics and bioassays for breast cancer management and conduct innovative clinical trials and population-based studies that can reduce the burden of disease in the Texas population. The annual direct peer-reviewed funding totals $5.4M, of which $3.2M (60%) is from NCI grants. Since the last competitive renewal, the program has authored 1,092 published papers: 562 (51%) represent intra-programmatic collaborations, 360 (33%) represent inter-programmatic collaborations, and 695 (64%) represent external collaborations. Forty-six percent of articles have appeared in journals with IF >5 and 18% have appeared in journals with IF >10, including Cancer Discov, Cell, JAMA, J Clin Oncol, Lancet Oncol, Nature, Nat Genet, and the N Engl J Med. Program members use all 14 shared resources. During the last grant period, research substantially influenced the clinical practice for treatment of bone metastasis from breast cancer. Another development was the Neo-Bioscore staging system, which improves upon the previously validated CPS+EG system and allows its application in patients with ERBB2-positive disease. The CPS+EG system influenced the incorporation of biological factors into the eighth edition of the American Joint Committee on Cancer breast cancer staging system. Program members have also made several impactful discoveries that improve our understanding of the mechanisms leading to subtypes of breast cancer, especially those with limited therapeutic options. Studies carried out via inter-programmatic collaborations on triple-negative breast cancers demonstrate a common evolutionary lineage along with a minor subpopulation of nonclonal cells, suggesting that the majority of copy-number aberrations are acquired at the earliest stages of tumor evolution (Gao R et al, Nat Genet, 2016); unveiling a molecular link among epithelial-mesenchymal transition, therapy resistance, and metastasis (Zhang J et al, Nat Cell Biol, 2013); and identifying iDAPK1 as a novel therapeutic strategy in triple- negative breast cancers with p53 mutations by modulating the mTOR/S6 pathway (Zhao J et al, J Clin Invest, 2015).

项目总结/摘要乳腺癌方案由来自25个部门的72名成员（60名主要成员，12名副成员）组成。该项目由Kelly K博士领导。Hunt，乳腺外科肿瘤学家和临床研究者; Khandan博士 Keyomarsi，实验室研究者; Debu Tripathy博士，乳腺肿瘤内科医生和临床调查员BrCP的主要科学目标是阐明癌症演变和转移的机制可以转化为乳腺癌患者的新治疗策略。有3个主题：1）遗传改变和乳腺癌的演变，2）已建立的乳腺癌的生物学，和3）靶向治疗，乳腺癌它们导致了3个具体目标：目标1：阐明分子和基因组进化乳腺癌发生和发展的基础;目的2：检测信号转导的失调，乳腺癌中的DNA修复、细胞周期和分化途径可能提供治疗靶点;目的 3：将科学发现用于乳腺癌管理的新疗法和生物测定，开展创新的临床试验和基于人群的研究，以减轻德克萨斯州的疾病负担。人口年度直接同行评审资金总额为540万美元，其中320万美元（60%）来自NCI赠款。自上一次竞争性更新以来，该计划已发表了1，092篇论文：562（51%）代表在项目内合作方面，360项（33%）为项目间合作，695项（64%）代表外部合作。46%的文章出现在IF >5的期刊上，18%的文章出现在IF > 5的期刊上。已经出现在IF >10的期刊上，包括Cancer Discov，Cell，JAMA，J Clin Oncol，Lancet Oncol，Nature， Nat Genet和N Engl J Med计划成员使用所有14个共享资源。在上一个资助期，研究实质上影响了治疗乳腺癌骨转移的临床实践。另一个发展是新的Bioscore分期系统，它改进了以前验证的 CPS+EG系统，并允许其应用于ERBB 2阳性疾病患者。CPS+EG系统影响了生物因素纳入第八版的美国联合委员会，癌症乳腺癌分期系统。项目成员还做出了几项有影响力的发现，提高我们对导致乳腺癌亚型的机制的理解，特别是那些具有有限治疗选择通过方案间合作开展的关于三阴性乳腺癌的研究证明了一个共同的进化谱系，沿着与非克隆细胞的一个小亚群，这表明大多数拷贝数畸变是在肿瘤发展的最早阶段获得的（Gao R等， Nat Genet，2016）;揭示了上皮-间充质转化、治疗抗性和转移（Zhang J等人，Nat Cell Biol，2013）;以及鉴定iDAPK 1作为三重-转移中的新治疗策略。通过调节mTOR/S6通路而导致具有p53突变的阴性乳腺癌（Zhao J等，J Clin Invest， 2015年）。