Mitochondrial catalase as a treatment for metastatic breast cancer

线粒体过氧化氢酶治疗转移性乳腺癌

• 批准号: 7707170
• 负责人: Warren C LADIGES
• 金额: $ 17.16万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7707170
• 关键词: Apoptosis; Applications Grants; Biological Models; Biological Process; Cells; Data; Development; Disease; Dose-Limiting; Drug Delivery Systems; Drug resistance; Goals; Immunohistochemistry; Inflammation; Mitochondria; Mus; Neoplasm Metastasis; System; Testing; Therapeutic Agents; Time; Tissues; Toxic effect; Transgenic Mice; Woman; angiogenesis; catalase; cell type; clinically relevant; design; malignant breast neoplasm; mouse model; novel; oxidative damage; prevent; public health relevance; tumor

DESCRIPTION (provided by applicant): The chance of developing invasive breast cancer during a woman's lifetime is approximately 1 in 8 and more than 40,000 women die of metastatic disease each year. Inherent or acquired tumor drug resistance and dose-limiting toxicity limit many agents used in the treatment of invasive breast cancer. Therefore, an important goal is the development of novel non-toxic therapeutic agents that are active against this deadly disease. We have preliminary data showing that mitochondrial catalase (mCAT) reduces metastatic progression of primary breast cancer in mice, suggesting that targeting mitochondria with catalase could be a potential strategy to treat or prevent metastatic breast cancer in women. The aims of this proposal are 1) to further characterize the ability of mCAT to suppress breast cancer metastasis in mice; and 2) develop an inducible system in mice for controlling the expression of mCAT in a time and cell dependent manner. The data generated in this proposal would confirm our preliminary observations and provide the rationale for developing and/or testing clinically relevant mitochondrial-specific drug delivery systems for treating metastatic breast cancer. PUBLIC HEALTH RELEVANCE: The project is designed to determine the ability of mitochondrially targeted catalase to suppress metastatic breast cancer in mice.

描述(申请人提供)：女性一生中患浸润性乳腺癌的几率约为八分之一，每年有40,000多名女性死于转移性疾病。固有的或获得性的肿瘤耐药性和剂量限制性毒性限制了许多药物用于浸润性乳腺癌的治疗。因此，开发对这种致命疾病有效的新型无毒治疗剂是一个重要的目标。我们有初步数据显示，线粒体过氧化氢酶(MCAT)可以减少小鼠原发性乳腺癌的转移进展，这表明以过氧化氢酶为靶点的线粒体可能是治疗或预防女性转移性乳腺癌的潜在策略。这项建议的目的是1)进一步鉴定MCAT抑制小鼠乳腺癌转移的能力；2)在小鼠中开发一种诱导系统，以时间和细胞依赖的方式控制MCAT的表达。这项提案中产生的数据将证实我们的初步观察，并为开发和/或测试临床相关的线粒体特异性药物输送系统治疗转移性乳腺癌提供理论基础。公共卫生相关性：该项目旨在确定线粒体靶向过氧化氢酶抑制小鼠转移性乳腺癌的能力。