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Targeting Breast Cancer Micrometastases: To Eliminate the Seeds of Evil

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Baylor College of Medicine Houston United States

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A substantial proportion of breast cancer patients develop metastases despite surgeries and adjuvant therapies. Metastasisis incurable and responsible for over 90 percent 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 influence scancer cells response to endocrine therapies. Specifically the three goals are 1 To assess the differential responses of bone micrometastases to adjuvant therapies as compared to their parental tumors in the mammary gland, and dissect if and how such differences are attributable to the interaction with their adjacent normal cells. 2 to further establish an experimental platform called Bone-in-culture array BICA that can mimic bone micrometastases and allow rapid testing of drug efficacies and 3 to perform drug screeningdiscoveries to identify compounds that can be combined with current standard-of-care and eradicate bone micrometastases.

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Technical Report,15 Mar 2018,14 Mar 2019



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Approved For Public Release;

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