Grant: Project Grant

Drs. McCaffrey, and Muller will investigate how breast cancer cells disrupt tissue barriers to escape the local environment, and how they subsequently evade elimination by the immune system. Project description Breast cancer develops from early stages that are localized and pose little immediate risk tothe patient. However, up to 50% can progress to potentially lethal forms of invasive breast cancer that move into surrounding normal tissue. Some cells in localized cancers are poised to become invasive, and additional mutations are not required. However, the surrounding normal tissue functions as a barrier and represses invasion of these cells. There are currently no tests that can predict which localized cancers will progress and there is concern of overtreatment. We predict that signals from localized breast cancers reprogram the initially repressive adjacent normal tissue to permit the transition to invasive breast cancer. To test this we will characterize how cancer cells alter the behavior of adjacent normal cells as they progress from localized to invasive cancer. We will test if these changes are functionally relevant by modifying cancer cells or normal cells to promote or suppress the invasive transition using animal models that accurately reproduce cancer progression in patients. We will also elucidate how cancer cells promote suppression of the immune system by looking at the types and activities of immune cells present and whether they function in an anti-cancer or pro-cancer capacity. Finally, we will explore approaches that reactivate the immune system to target and eliminate localized cancer cells that try to escape and invade surrounding tissue. Impact and Relevance A better understanding of how cancers initiate and progress is crucial to develop tests that can guide doctors and patients for treatment decisions, as well as to identify new disease biomarkers and therapeutic targets for preventative treatment.