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Review ArticleReview Article

Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer: A Review

Edris Choupani, Mohammad Mahmoudi Gomari, Saeed Zanganeh, Sherko Nasseri, Kaveh Haji-allahverdipoor, Neda Rostami, Yaeren Hernandez, Safa Najafi, Neda Saraygord-Afshari and Arshad Hosseini
Michael Gottesman, ASSOCIATE EDITOR
Pharmacological Reviews March 2023, 75 (2) 309-327; DOI: https://doi.org/10.1124/pharmrev.122.000665
Edris Choupani
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Mohammad Mahmoudi Gomari
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Saeed Zanganeh
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Sherko Nasseri
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Kaveh Haji-allahverdipoor
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Neda Rostami
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Yaeren Hernandez
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Safa Najafi
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Neda Saraygord-Afshari
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Arshad Hosseini
Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran (E.C., M.M.G., N.S.-A., A.H.); Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran (S.Z.); Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran (S.N., K.H.-a.); Department of Chemical Engineering, Faculty of Engineering, Arak University, Iran (N.R.); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona (Y.H.); and Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran (S.N.)
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Michael Gottesman
Roles: ASSOCIATE EDITOR
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Abstract

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Expression of androgen receptor (AR) in carcinoma cells has been observed in a subset of patients with TNBC; therefore, inhibiting androgen signaling pathways holds promise for TNBC targeting. The new AR inhibitors have opened up new therapy possibilities for BC patients carrying AR-positive TNBC cells. Our group provides a comprehensive review of the structure and function of the AR and clinical evidence for targeting the cell’s nuclear receptor in TNBC. We updated AR agonists, inhibitors, and antagonists. We also presented a new era of genetic manipulating CRISPR/Cas9 and nanotechnology as state-of-the-art approaches against AR to promote the efficiency of targeted therapy in TNBC.

Significance Statement The lack of effective treatment for triple-negative breast cancer is a health challenge. The main disadvantages of existing treatments are their side effects, due to their nonspecific targeting. Molecular targeting of cellular receptors, such as androgen receptors, increased expression in malignant tissues, significantly improving the survival rate of breast cancer patients.

Footnotes

    • Received June 7, 2022.
    • Revision received September 26, 2022.
    • Accepted October 31, 2022.
  • This article received no external funding.

  • No author has an actual or perceived conflict of interest with the contents of this article.

  • dx.doi.org/10.1124/pharmrev.122.000665.

  • Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 75 (2)
Pharmacological Reviews
Vol. 75, Issue 2
1 Mar 2023
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Review ArticleReview Article

Targeted Therapies Against the Androgen Receptor in TNBC

Edris Choupani, Mohammad Mahmoudi Gomari, Saeed Zanganeh, Sherko Nasseri, Kaveh Haji-allahverdipoor, Neda Rostami, Yaeren Hernandez, Safa Najafi, Neda Saraygord-Afshari and Arshad Hosseini
Pharmacological Reviews March 1, 2023, 75 (2) 309-327; DOI: https://doi.org/10.1124/pharmrev.122.000665

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Review ArticleReview Article

Targeted Therapies Against the Androgen Receptor in TNBC

Edris Choupani, Mohammad Mahmoudi Gomari, Saeed Zanganeh, Sherko Nasseri, Kaveh Haji-allahverdipoor, Neda Rostami, Yaeren Hernandez, Safa Najafi, Neda Saraygord-Afshari and Arshad Hosseini
Pharmacological Reviews March 1, 2023, 75 (2) 309-327; DOI: https://doi.org/10.1124/pharmrev.122.000665
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  • Article
    • Visual Overview
    • Abstract
    • I. Introduction
    • II. TNBC Subtypes and Their Clinical Characteristics
    • III. Biologic Characteristics of Androgen Receptor
    • IV. A Glimpse to Androgen Receptor in Prostate Cancer
    • V. The Androgen Receptor Signaling Pathway in Triple-Negative Breast Cancer
    • VI. Androgen Receptor Targeting in Triple-Negative Breast Cancer
    • VII. Genome Editing Against Androgen Receptor-Positive Cells: CRISPR/cas9 Enters the Scene
    • VIII. Overcoming Drug Resistance in Triple-Negative Breast Cancer by Nanotechnology
    • IX. Conclusions and Future Perspectives
    • Acknowledgments
    • Authorship Contributions
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