Breast Cancer Stem Cells: Responsible for Therapeutic Resistance and Relapse?

Abstract

Since the “war on cancer” was waged more than 30 years ago, the fact remains that the metastatic breast cancer is still incurable and patients will ultimately die from this disease [1]. American Cancer Society has estimated that in the year 2012, there will be about 229,060 new cases of breast cancer and an estimated 39,920 new deaths caused by breast cancer in the United States alone [2]. Majority of breast cancer-related deaths are primarily due to metastatic disease which display poor prognosis with an estimated 5-year survival of ~20 %. Furthermore, therapeutic resistance and relapse are strongly associated with metastatic disease in breast cancer patients [1]. Despite the fact that the heterogeneity of tumor cells had been widely acknowledged, it has not been validated until the 1990s due to lack of markers and techniques. D. Bonnet and J. Dick were the first to describe the hierarchical organization of acute myeloid leukemia (AML) and the existence of cancer stem cells (CSC). This was quickly followed by the identification of CSCs from number of malignancies enabling us to better characterize these cells in mouse models and preclinical settings. These ongoing functional studies suggested that CSCs may explain the failure to treat advance metastatic tumors. Thus the “seed and soil” hypothesis proposed by Stephen Paget more than 120 years ago may re-framed in a modern context explaining the ability of subset of tumor cells “seed” or “CSCs” to disseminate and metastasize to secondary organs where nutrient-rich microenvironment “soil” stimulates the secondary tumor growth by enhancing CSC self-renewal.