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（由申请人提供）：女性一生中发生浸润性乳腺癌的几率约为1/8，每年有超过40，000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用于治疗浸润性乳腺癌的药物。因此，一个重要的目标是开发对这种致命疾病有活性的新型无毒治疗剂。我们有初步数据显示，线粒体过氧化氢酶（mCAT）减少小鼠原发性乳腺癌的转移进展，这表明用过氧化氢酶靶向线粒体可能是治疗或预防女性转移性乳腺癌的潜在策略。该提案的目的是1）进一步表征mCAT抑制小鼠乳腺癌转移的能力;和2）在小鼠中开发用于以时间和细胞依赖性方式控制mCAT表达的诱导型系统。本提案中生成的数据将证实我们的初步观察结果，并为开发和/或测试用于治疗转移性乳腺癌的临床相关的乳腺癌特异性药物递送系统提供依据。公共卫生关系：该项目旨在确定肿瘤靶向过氧化氢酶抑制小鼠转移性乳腺癌的能力。