Mitochondrial catalase as a treatment for metastatic breast cancer

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八分之一，每年有超过40,000名女性死于转移性疾病。固有或获得性肿瘤耐药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新的无毒治疗药物，有效对抗这种致命的疾病。我们的初步数据显示，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。本研究的目的是：1)进一步表征mCAT抑制小鼠乳腺癌转移的能力；2)在小鼠中建立一个诱导系统，以时间和细胞依赖的方式控制mCAT的表达。该提案中产生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线粒体特异性药物传递系统提供理论依据。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。

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.