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Modifying the Stromal Microenvironment to Reduce Breast Cancer Metastasis

Developmental Research Project:
Modifying the Stromal Microenvironment to Reduce Breast Cancer Metastasis

Principal Investigator: Zena Werb, PhD
Institution: UCSF Department of Anatomy

Abstract:
Elevated levels of stromal collagen, (observed in women with mammographically dense breasts), or collagen cross linkers such as lysyl oxidase promote breast tumor progression by stiffening the matrix. Individuals pre disposed to fibrosis including African Americans (enhanced keloids), women with mammographically dense breasts with elevated collagen, or women with elevated tissue glycation due to uncontrolled diabetes constitute cancer prone "at risk" populations that merit intensified clinical surveillance. Collagen and its cross-linking accompanies tissue fibrosis and fibrosis and increases risk of malignancy and generates a poorer prognosis. Previous studies have shown that stromal fibroblasts regulate the distribution of fibrillar collagen in tumors. In this project we propose to target the stromal fibroblast population directly by a drug that has shown efficacy against fibrosis and examine how that affect the progression of basal/TNBC in mouse models. Our approach to this problem is to target the desmoplasia/fibrosis in breast cancer. We have initiated a study aimed to target the stromal fibroblast population directly by a drug that has shown efficacy against fibrosis and examine how that affects the progression of basal/ triple negative breast cancer (TNBC) in mouse models.. Our preliminary data suggest that the drug strongly inhibits proliferation of CAFs and promotes their cell death, but not epithelial tumor cells. Thus, these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics.