Grant: Operating Grant

One in eight women in North America is expected to be diagnosed with breast cancer in her lifetime. Approximately one in six of these women will die from it. Progression of breast cancer to metastasis is responsible for most of these fatalities. Unfortunately, we still do not fully understand the processes by which tumors metastasize. Additionally, there are limited options to prevent metastases and stop breast cancer in its tracks. What we do know is that breast cancer cells need to acquire multiple abnormal characteristics to grow in a rapid, uncontrolled manner, and migrate out of the primary tumor to establish themselves in distant organs. They also cannot do this alone, and require the help of healthy surrounding cells to sustain these processes. Yet the precise nature of these interactions remains unclear. It is therefore critically important to advance our understanding of these processes to maximize treatment efficacy for breast cancer patients. The production of certain proteins is key for cancer cells to grow, form tumors, and spread. We have recently discovered that a master regulator of protein synthesis, called eIF4E, must be activated (phosphorylated) for cancer cells to produce such proteins. Indeed, mice genetically engineered to be unable to activate eIF4E are resistant to cancer development. We also have promising new data suggesting that this activation of eIF4E is imperative for cancer cells and healthy cells to interact and promote metastasis. This project therefore aims to fully determine whether eIF4E activation allows breast cancer to progress to metastasis. We will identify the mechanism through which this occurs and most importantly, we will test a newly identified drug that blocks eIF4E activation to determine its potential as a novel therapeutic for breast cancer. We anticipate that this drug will also be effective in preventing breast cancer metastasis, hopefully leading to life-saving treatments.