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

• 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
• 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

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.

项目摘要 我，莱恩·科布博士，是爱荷华州大学的助理研究员。我打算从事 作为一名独立研究员，在学术研究机构担任终身教职， 我可能会继续我在爱荷华州大学训练期间所做的研究。我 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应用程序侧重于这项研究的一个方面;如何 肥胖相关的炎症驱动乳腺癌的进展。这项研究旨在解决一个未得到满足的 癌症领域的问题。虽然肥胖和乳腺癌进展之间的联系以及更糟糕的临床表现， 结果是明确的，没有开发出治疗肥胖患者的特异性疗法， 由于肥胖相关的并发症，肥胖患者经常被排除在临床试验之外。目标1， 这项提案将确定ANGPTL 4在肥胖驱动的乳腺癌进展中的作用，并提供 ANGPTL 4靶向疗法治疗肥胖乳腺癌患者的基本原理。目标2将测试 在肥胖驱动的乳腺癌进展的临床前模型中靶向ANGPTL 4并表征新的 抗人ANGPTL 4抗体抑制ANGPTL 4的能力。这些目标将共同促进 开发ANGPTL 4抗体作为改善肥胖乳腺癌结局的疗法 患者K22奖将有助于我实现转变为独立癌症研究人员的目标。 这个奖项将使我能够在临床癌症研究方面继续深造。作为一名基础科学家， 过渡到一个独立的职业生涯，更大的重点是转化癌症研究，这种培训将 非常有益。我计划成功过渡到一个独立的职位，并建立一个独立的 研究计划包括在该奖项的第一年年底前申请R 01。拟议 本K22应用程序中的目标将为我构建R 01提供坚实的基础 应用程序.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 极大地帮助我建立了一个成功的和有影响力的职业生涯作为一个翻译癌症研究人员， 肿瘤微环境领域。