Therapeutic Implications of Cellular Heterogeneity and Plasticity in Breast Cancer

Cellular heterogeneity represents one of the greatest challenges in cancer therapeutics. In many malignancies, this heterogeneity is generated during tumor evolution through a combination of genetic alterations and epigenetic events that recapitulate normal developmental processes including stem cell self-renewal and differentiation. Many, if not most, tumors display similar hierarchal organization, at the apex of which are stem-like cells'' that drive tumor growth, mediate metastasis, and contribute to treatment resistance. Using breast cancer as a model, we discuss how an improved understanding of tumor cellular heterogeneity and plasticity may lead to development of more effective therapeutic strategies.