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Targeting the Stem Cell Properties of Adult Breast Cancer Cells: Using Combinatorial Strategies to Overcome Drug Resistance

  • Molecular Biotechnology of Adult Stem Cells (G Stein, Section Editor)
  • Published:
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Abstract

Purpose of Review

Cancer is a major public health problem worldwide. In aggressive cancers, which are heterogeneous in nature, there exists a paucity of targetable molecules that can be used to predict outcome and response to therapy in patients, especially those in the high-risk category with a propensity to relapse following chemotherapy. This review addresses the challenges pertinent to treating aggressive cancer cells with inherent stem cell properties, with a special focus on triple-negative breast cancer (TNBC).

Recent Findings

Plasticity underlies the cancer stem cell (CSC) phenotype in aggressive cancers like TNBC. Progenitors and CSCs implement similar signaling pathways to sustain growth, and the convergence of embryonic and tumorigenic signaling pathways has led to the discovery of novel oncofetal targets, rigorously regulated during normal development, but aberrantly reactivated in aggressive forms of cancer.

Summary

Translational studies have shown that Nodal, an embryonic morphogen, is reactivated in aggressive cancers, but not in normal tissues, and underlies tumor growth, invasion, metastasis, and drug resistance. Front-line therapies do not inhibit Nodal, but when a combinatorial approach is used with an agent such as doxorubicin followed by anti-Nodal antibody therapy, significant decreases in cell growth and viability occur. These findings are of special interest in the development of new therapeutic interventions that target the stem cell properties of cancer cells to overcome drug resistance and metastasis.

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Acknowledgements

Supported by the National Institute of General Medical Sciences U54GM104942 (NVM, EAS, REBS) and NIH/NCI R37CA59702 and RO1CA121205 (MJCH).

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Authors and Affiliations

  1. Department of Biochemistry, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV, 26506, USA

    Naira V. Margaryan, Elisabeth A. Seftor & Richard E.B. Seftor

  2. Cancer Institute, West Virginia University, Morgantown, WV, 26506, USA

    Naira V. Margaryan, Elisabeth A. Seftor, Richard E.B. Seftor & Mary J.C. Hendrix

  3. Department of Biology, Shepherd University, P.O. Box 5000, 301 N. King St, Shepherdstown, WV, 25443, USA

    Naira V. Margaryan, Elisabeth A. Seftor, Richard E.B. Seftor & Mary J.C. Hendrix

  4. Department of Internal Medicine, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV, 26506, USA

    Mary J.C. Hendrix

Authors
  1. Naira V. Margaryan
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  2. Elisabeth A. Seftor
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Corresponding author

Correspondence to Mary J.C. Hendrix.

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Conflict of Interest

Naira V. Margaryan declares that she has no conflicts of interest. Elisabeth A. Seftor, Richard E.B. Seftor, and Mary J.C. Hendrix are listed as co-inventors on Nodal-related patents and/or disclosures.

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This article does not contain any raw data with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Molecular Biotechnology of Adult Stem Cells

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Margaryan, N.V., Seftor, E.A., Seftor, R.E. et al. Targeting the Stem Cell Properties of Adult Breast Cancer Cells: Using Combinatorial Strategies to Overcome Drug Resistance. Curr Mol Bio Rep 3, 159–164 (2017). https://doi.org/10.1007/s40610-017-0067-5

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  • DOI: https://doi.org/10.1007/s40610-017-0067-5

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