Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy.
Recent research in breast biology has provided support for the cancer stem-cell hypothesis. Two important components of this hypothesis are that tumors originate in mammary stem or progenitor cells as a result of dysregulation of the normally tightly regulated process of self-renewal. As a result, tumors contain and are driven by a cellular subcomponent that retains key stem-cell properties including self-renewal, which drives tumorigenesis and differentiation that contributes to cellular heterogeneity. Advances in stem-cell technology have led to the identification of stem cells in normal and malignant breast tissue. The study of these stem cells has helped to elucidate the origin of the molecular complexity of human breast cancer. The cancer stem-cell hypothesis has important implications for early detection, prevention, and treatment of breast cancer. Both hereditary and sporadic breast cancers may develop through dysregulation of stem-cell self-renewal pathways. These aberrant stem cells may provide targets for the development of cancer prevention strategies. Furthermore, because breast cancer stem cells may be highly resistant to radiation and chemotherapy, the development of more effective therapies for this disease may require the effective targeting of this cell population.
University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109-5942, USA.
Madhuri
M
Kakarala
Max S
MS
Wicha
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011878:Radiotherapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D017211:Treatment Failure; D051153:Wnt Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; D051880:Receptors, Notch; D051153:Wnt Proteins