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Recent developments in targeting breast cancer stem cells (BCSCs): a descriptive review of therapeutic strategies and emerging therapies

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Abstract

Despite recent advancements in the diagnosis and treatment of breast cancer (BC), patient outcomes in terms of survival, recurrence, and disease progression remain suboptimal. A significant factor contributing to these challenges is the cellular heterogeneity within BC, particularly the presence of breast cancer stem cells (BCSCs). These cells are thought to serve as the clonogenic nexus for new tumor growth, owing to their hierarchical organization within the tumor. This descriptive review focuses on the evolving strategies to target BCSCs, which have become a pivotal aspect of therapeutic development. We explore a variety of approaches, including targeting specific tumor surface markers (CD133 and CD44), transporters, heat shock proteins, and critical signaling pathways like Notch, Akt, Hedgehog, KLF4, and Wnt/β-catenin. Additionally, we discuss the modulation of the tumor microenvironment through the CXCR-12/CXCR4 axis, manipulation of pH levels, and targeting hypoxia-inducible factors, vascular endothelial growth factor, and CXCR1/2 receptors. Further, this review focuses on the roles of microRNA expression, strategies to induce apoptosis and differentiation in BCSCs, dietary interventions, dendritic cell vaccination, oncolytic viruses, nanotechnology, immunotherapy, and gene therapy. We particularly focused on studies reporting identification of BCSCs, their unique properties and the efficacy of various therapeutic modalities in targeting these cells. By dissecting these approaches, we aim to provide insights into the complex landscape of BC treatment and the potential pathways for improving patient outcomes through targeted BCSC therapies.

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  1. Khubaib Ali and Muhammad Nabeel have contributed equally to this work and shared the first authorship.

Authors and Affiliations

  1. Department of Clinical Pharmacy, Akhtar Saeed College of Pharmaceutical Sciences, Bahria Town, Lahore, Pakistan

    Khubaib Ali & Muhammad Nabeel

  2. Department Clinical Oncology Pharmacy, Cancer Care Hospital & Research Centre, Lahore, Pakistan

    Khubaib Ali & Muhammad Nabeel

  3. Department of Biological Sciences, KAM School of Life Sciences, Forman Christian College (A Chartered University), Lahore, Pakistan

    Fatima Mohsin

  4. Department of Bio-Technology, Lahore College for Women University, Jail Road, Lahore, Pakistan

    Mehwish Iqtedar

  5. Department of Pharmaceutics, College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, Pakistan

    Muhammad Islam, Furqan K. Hashmi & Hamid Saeed

  6. Faculty of Pharmacy, Bahauddin Zakariya University, Bason Road, Multan, Pakistan

    Muhammad Fawad Rasool

  7. AG & Associates, Street NE, Calgary, AB, T2A 6T2, Canada

    Syed Ahmed Hussain

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Contributions

First two authors contributed equally to this work. KA and MN wrote the manuscript and conceived the idea, edited the manuscript and worked on nano-technology approaches, gene therapy and immunotherapy and diet mediate therapy. FM provided in-depth information about the signaling pathways and made that figure, and edited the manuscript; MIQ and MI contributed in providing valuable information on surface receptors and transporters, revised the manuscript, and tabulated the studies on nanocarriers; MFR and FKH edited the manuscript and wrote tumor microenvironment and miRNA-based approaches; SAH prepared figures for the manuscript and edited the manuscript; HS supervised the work, edited the manuscript and tabulated the results on surface receptor targeting, and provided literature searches. All authors read and approved the manuscript.

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Correspondence to Hamid Saeed.

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Ali, K., Nabeel, M., Mohsin, F. et al. Recent developments in targeting breast cancer stem cells (BCSCs): a descriptive review of therapeutic strategies and emerging therapies. Med Oncol 41, 112 (2024). https://doi.org/10.1007/s12032-024-02347-z

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