Targeting ANGPTL4 in obesity-driven breast cancer progression

靶向 ANGPTL4 在肥胖驱动的乳腺癌进展中的作用

基本信息

批准号：
9742858
负责人：
Ryan H Kolb
金额：
$ 17.97万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9742858
关键词：
ANGPTL4 gene Address Adipocytes Affect Angiogenesis Inhibitors Angiogenic Factor Animal Model Antibodies Automobile Driving Avastin Award Breast Breast Cancer Model Breast Cancer Patient Breast Cancer Treatment Cancer Biology Cells Clinical Clinical Trials Data Development Disease Progression Effectiveness Estrogen receptor positive Faculty Foundations Gap Junctions Goals Human Incidence Inflammasome Inflammation Institution Interleukin-1 beta Iowa K22 Award Light Link Malignant Neoplasms Mammary Gland Parenchyma Menopause Modeling Monoclonal Antibodies Mus Non obese Obesity Outcome Patients Peptide Signal Sequences Positioning Attribute Postmenopause Pre-Clinical Model Publications Research Research Assistant Research Personnel Research Training Risk Factors Role Scientist Signal Transduction Solid Testing Tissues Training Transplantation Tumor Angiogenesis Tumor-associated macrophages Universities Up-Regulation Vascular Endothelial Growth Factors Woman Work angiogenesis anticancer research bevacizumab breast cancer progression cancer type career conditional knockout effectiveness testing efficacy testing experimental study improved improved outcome innovation macrophage malignant breast neoplasm mouse model novel obesity treatment pre-clinical prevent programs response standard of care targeted treatment tenure track therapeutic target therapy development translational cancer research tumor tumor immunology tumor microenvironment tumor progression tumorigenesis

项目摘要

Project Summary I, Dr. Ryan Kolb, am an assistant research scientist at the University of Iowa. I plan to pursue a career as an independent researcher with a tenure-track faculty position at an academic research institution, so that I may continue my research that I have developed during my training at the University of Iowa. My research focuses on how interactions between cells in the tumor microenvironment affect tumorigenesis and disease progression. This K22 application focuses on one aspect of this research; how obesity-associated inflammation drives breast cancer progression. This research seeks to addresses an unmet problem in the cancer field. While, the link between obesity and breast cancer progression and a worse clinical outcome are well established, there has been no specific therapies developed to treat obese patients and obese patients are often excluded from clinical trials due to obesity-related complications. In Aim 1 of this proposal we will define the role of ANGPTL4 in obesity-driven breast cancer progression and provide a rationale for ANGPTL4 targeted therapies to treat obese breast cancer patients. Aim 2 will test the efficacy of targeting ANGPTL4 in preclinical models of obesity-driven breast cancer progression and characterize novel anti-human ANGPTL4 antibodies for their ability to inhibit ANGPTL4. Together these aims will promote the development of ANGPTL4 antibodies as a therapy to improve the outcome for obese breast cancer patients. The K22 award will be beneficial in my goal to transition into an independent cancer researcher. This award will allow me to pursue further training in clinical cancer research. As a basic scientist looking to transition into an independent career with a larger focus on translational cancer research, this training will be highly beneficial. My plan to successfully transition to an independent position and establish an independent research program involves applying for an R01 by the end of the first year of this award. The proposed aims in this K22 application will provide me with a solid foundation upon which to build a R01 application. Combined with my background in cancer biology and cancer immunology, this K22 award will greatly aid me in establishing a successful and impactful career as a translational cancer researcher in the tumor microenvironment field.

项目概要我，Ryan Kolb 博士，是爱荷华大学的助理研究科学家。我打算追求职业生涯作为在学术研究机构中拥有终身教职的独立研究员，我可以继续我在爱荷华大学培训期间开展的研究。我的研究重点是肿瘤微环境中细胞之间的相互作用如何影响肿瘤发生和疾病进展。这个 K22 应用程序重点关注这项研究的一个方面；如何肥胖相关炎症会促进乳腺癌进展。这项研究旨在解决一个未满足的问题癌症领域的问题。同时，肥胖与乳腺癌进展之间的联系以及更糟糕的临床症状结果已明确，目前还没有开发出治疗肥胖患者的具体疗法，由于肥胖相关并发症，肥胖患者常常被排除在临床试验之外。目标 1 在这项提案中，我们将定义 ANGPTL4 在肥胖驱动的乳腺癌进展中的作用，并提供 ANGPTL4 靶向疗法治疗肥胖乳腺癌患者的基本原理。目标2将测试效果在肥胖驱动的乳腺癌进展的临床前模型中靶向 ANGPTL4 并表征新的抗人 ANGPTL4 抗体具有抑制 ANGPTL4 的能力。这些目标共同将促进开发 ANGPTL4 抗体作为改善肥胖乳腺癌预后的疗法患者。 K22 奖项将有助于我实现成为一名独立癌症研究员的目标。该奖项将使我能够继续接受临床癌症研究方面的进一步培训。作为一名基础科学家过渡到独立职业，更加关注转化癌症研究，该培训将非常有益。我计划成功过渡到独立职位并建立独立的研究计划涉及在该奖项第一年年底之前申请 R01。拟议的这个 K22 应用程序的目标将为我构建 R01 奠定坚实的基础应用。结合我在癌症生物学和癌症免疫学方面的背景，这个 K22 奖将作为一名转化癌症研究员，极大地帮助我建立了成功且有影响力的职业生涯肿瘤微环境领域。