Cancer malignancies continually adapt to the changing epithelium and the surrounding tumor microenvironment, or stroma, in order to survive and spread outside of the primary tissue. In normal human mammary glands, the epithelium is highly organized. These glands have intact lumens, an intact basement membrane, and surrounding stromal cells. During cancer progression, some of these cells undergo progressive changes. Tumors develop by utilizing normal developmental processes to promote survival and poor prognosis in patients. At each stage of tumor progression, the epithelium becomes exposed to a completely different set of cells and molecules, depending on its neighbors. This microenvironment promotes changes within the epithelium. This context is critical in being able to understand cancer and develop effective therapies.
We use integrated biological approaches to understand the contributions of specific genes in vivo at multiple points in cancer progression, spanning from normal mammary development to tumor progression to metastasis to chemotherapy resistance.
We both develop and use a combination of mouse and human xenograft in vivo models, cell culture and organotypic cultures, and systems biology approaches to study biomarkers of epithelial plasticity and to determine how these genes drive aberrations in fundamental biological processes, e.g., differentiation state, progenitor cell maintenance, metabolism, and genomic integrity.
We also are identifying targeted therapies appropriate for personalized treatment of cancer patients based on these biomarkers. This research is translational and relevant to both cancer prevention and treatment of poor prognosis in cancer patients.