Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Sep 1;28(25):4006-12.
doi: 10.1200/JCO.2009.27.5388. Epub 2010 May 24.

Targeting breast cancer stem cells

Suling Liu  1 , Max S Wicha
Affiliations
Review

Targeting breast cancer stem cells

Suling Liu et al. J Clin Oncol. .

Abstract

There is increasing evidence that many cancers, including breast cancer, contain populations of cells that display stem-cell properties. These breast cancer stem cells, by virtue of their relative resistance to radiation and cytotoxic chemotherapy, may contribute to treatment resistance and relapse. The elucidation of pathways that regulate these cells has led to the identification of potential therapeutic targets. A number of agents capable of targeting breast cancer stem cells in preclinical models are currently entering clinical trials. Assessment of the efficacy of the agents will require development of innovative clinical trial designs with appropriate biologic and clinical end points. The effective targeting of breast cancer stem cells has the potential to significantly improve outcome for women with both early-stage and advanced breast cancer.

PubMed Disclaimer

Conflict of interest statement

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

Figures

Fig 1.
Fig 1.
Targeting signal transduction pathways in breast cancer stem cells. Schematic illustration of key signal transduction pathways, therapeutic targets, and targeting agents (shown in red). These pathways include Notch; Hedgehog; Wnt; human epidermal growth factor receptor 2 (HER2) –Akt; and cytokine loops, including interleukin (IL) -6 and IL-8.
Fig 2.
Fig 2.
Effects of cancer stem cell (CSC) –targeting agents when administered in advanced versus adjuvant settings. (A) Model illustrating hypothetical effect of administration of a selective CSC therapeutic agent in advanced versus adjuvant setting. Only modest effects on tumor size and growth rate are observed when CSC-targeting agent is administered in the advanced setting. In contrast, in the adjuvant setting, eliminating CSCs prevents tumor recurrence. (B) Clinical efficacy of human epidermal growth factor receptor 2 (HER2) blockade in advanced versus adjuvant setting. Hypothetical models illustrate the relationship between HER2 expression in CSC and bulk tumor population and efficacy of HER2 blockade in advanced and adjuvant settings. In tumors classified as HER2-positive (ie, immunohistochemistry [IHC] 3+ or fluorescence in situ hybridization [FISH] positive), HER2 is expressed in both CSC and bulk tumor populations. In these tumors, HER2-targeting agents demonstrate clinical efficacy when administered in both advanced (tumor regression) and adjuvant (reduced recurrence) settings. In tumors currently classified as HER2-negative (ie, IHC1/2+ or FISH negative), HER2 may be selectively expressed in CSC but not bulk cell populations. In these tumors, HER2-targeting agents may be effective when administered in adjuvant but not advanced settings. In contrast, in truly HER2-negative tumors (HER2 0 by IHC), HER2-targeting agents would be predicted to be ineffective in both adjuvant and advanced settings.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353:1784–1792. - PubMed
    1. Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–134. - PubMed
    1. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–3988. - PMC - PubMed
    1. Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–567. - PMC - PubMed
    1. Charafe-Jauffret E, Ginestier C, Iovino F, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 2009;69:1302–1313. - PMC - PubMed