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Targeting Breast Cancer Micrometastases: To Eliminate the Seeds of Evil
A substantial proportion of breast cancer patients develop metastases despite surgeries and adjuvant therapies. Metastasis is incurable and responsible for over 90% of breast cancer-related death. Thus, the prevention of metastasis is an imperative clinical need. We seek to understand how microscopic metastases in distant organs (e.g., bone), before becoming overt malignancies, survive and progress by interacting with specific normal cells in that organ. The rationale is that such interaction may confer resistance to current adjuvant therapies and may also render the cancer cells vulnerable to novel treatments. To date, very few pre-clinical models of micrometastases exist. We have filled this gap by developing a series of techniques that allow us to monitor and quantitate the progression of micrometastases. In this application, we will further establish the authenticity of these models in reflecting biological properties of micrometastases. We will also use them to identify therapies that may eliminate metastatic seeds, especially in the bone. We will examine all breast cancer subtypes with an emphasis on estrogen receptor-positive breast cancer and investigate how the bone environment influences cancer cells response to endocrine therapies.
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