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.
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Michael D
MD
Brooks
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Monika L
ML
Burness
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mwicha@umich.edu.
Max S
MS
Wicha
D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D063646:Carcinogenesis / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology; D059016:Tumor Microenvironment