Targeting breast cancer micrometastases: to eliminate the seeds of evil
Abstract
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. 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 screening/discoveries to identify compounds that can be combined with current standard-of-care and eradicate bone micrometastases. The fulfillment of these goals will provide novel strategies that may significantly reduce bone or possibly other metastases
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2020
- Accession Number
- AD1104089
Entities
People
- Xiang Zhang
Organizations
- Baylor College of Medicine