Chemo Resistance of Breast Cancer Stem Cells
Final rept. 2 Apr 2004-1 Apr 2007
MICHIGAN UNIV ANN ARBOR
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There is increasing evidence that breast cancers are driven by a small subcomponent that displays stem cell properties. We hypothesize that these breast cancer stem cells are resistant to chemotherapy and may contribute to tumor relapse. In order to provide evidence for this, we determined the effect of chemotherapeutic agents on breast cancer stem cell populations in primary mouse xenografts. Tumor regression induced by these chemotherapeutic agents is accompanied by an enrichment in cancer stem cells as determined by the stem cell marker CD44 CD24- and Aldehyde dehydrogenase. In order to determine the clinical relevance of these studies, we have examined expression of these markers in patients receiving neoadjuvant therapy utilizing pre- and post-treatment biopsies. In two separate studies, one completed at the University of Michigan and one in collaboration with Baylor College of Medicine, we demonstrate that tumor shrinkage from neoadjuvant chemotherapy is associated with an increase in the percent of stem cells in residual tumors. These studies provide support for the cancer stem cell hypothesis and suggest that more effective therapies against breast cancer will require the development of strategies to target and eliminate the cancer stem cell population.
- Anatomy and Physiology
- Medicine and Medical Research