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Review
. 2008 Jun 10;26(17):2813-20.
doi: 10.1200/JCO.2008.16.3931.

Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy

Madhuri Kakarala  1 , Max S Wicha
Affiliations
Review

Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy

Madhuri Kakarala et al. J Clin Oncol. .

Abstract

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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Authors' Disclosures of Potential Conflicts of Interest: Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: Max S. Wicha, OncoMed Pharmaceuticals (C) Stock Ownership: Max S. Wicha, OncoMed Pharmaceuticals Honoraria: None Research Funding: Max S. Wicha, Merck Expert Testimony: None Other Remuneration: None

Figures

Fig 1
Fig 1
Clinical interventions targeting stem cells (SCs) for cancer prevention and treatment. Cancers arise through dysregulation of SC self-renewal pathways. This produces tumors driven by a cancer SC component. Shown are strategies for cancer risk reduction, early detection, primary prevention, and treatment based on targeting the SC population. ER, estrogen receptor.
Fig 2
Fig 2
Self-renewal and differentiation pathways in breast stem cells. Both hereditary and sporadic breast cancers may originate in breast stem/progenitor cells through dysregulation of the normally tightly regulated process of stem-cell self-renewal. This may result from loss of BRCA1 function in hereditary breast cancers. In sporadic cancers this may result from loss of PTEN or activation of the human epidermal growth factor receptor 2, Notch, or Hedgehog pathways. This results in clonal expansion of stem cells providing targets for further carcinogenic events.
See this image and copyright information in PMC

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