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      Cancer stem cells and their niche in cancer progression and therapy

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          Abstract

          High recurrence and metastasis rates and poor prognoses are the major challenges of current cancer therapy. Mounting evidence suggests that cancer stem cells (CSCs) play an important role in cancer development, chemoradiotherapy resistance, recurrence, and metastasis. Therefore, targeted CSC therapy has become a new strategy for solving the problems of cancer metastasis and recurrence. Since the properties of CSCs are regulated by the specific tumour microenvironment, the so-called CSC niche, which targets crosstalk between CSCs and their niches, is vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. In this review, we aim to highlight the factors within the CSC niche that have important roles in regulating CSC properties, including the extracellular matrix (ECM), stromal cells (e.g., associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and mesenchymal stem cells (MSCs)), and physiological changes (e.g., inflammation, hypoxia, and angiogenesis). We also discuss recent progress regarding therapies targeting CSCs and their niche to elucidate developments of more effective therapeutic strategies to eliminate cancer.

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          Evolution of the cancer stem cell model.

          Genetic analyses have shaped much of our understanding of cancer. However, it is becoming increasingly clear that cancer cells display features of normal tissue organization, where cancer stem cells (CSCs) can drive tumor growth. Although often considered as mutually exclusive models to describe tumor heterogeneity, we propose that the genetic and CSC models of cancer can be harmonized by considering the role of genetic diversity and nongenetic influences in contributing to tumor heterogeneity. We offer an approach to integrating CSCs and cancer genetic data that will guide the field in interpreting past observations and designing future studies. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Cancer stem cells revisited.

            The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their identification and eradication has not been as obvious as was initially hoped. Recently developed lineage-tracing and cell-ablation strategies have provided insights into CSC plasticity, quiescence, renewal, and therapeutic response. Here we discuss new developments in the CSC field in relationship to changing insights into how normal stem cells maintain healthy tissues. Expectations in the field have become more realistic, and now, the first successes of therapies based on the CSC concept are emerging.
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              Targeting cancer stem cell pathways for cancer therapy

              Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.
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                Author and article information

                Contributors
                jpwang06@126.com
                xiaoyanli5959@163.com
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                1 December 2023
                1 December 2023
                2023
                : 23
                : 305
                Affiliations
                [1 ]Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, ( https://ror.org/00jjkh886) Zhoukou, 466001 Henan China
                [2 ]GRID grid.263452.4, ISNI 0000 0004 1798 4018, Department of General Surgery, , Shanxi Province Cancer Hospital, Affiliated of Shanxi Medical University, ; Taiyuan, 030013 Shanxi China
                [3 ]Department of Ultrasound, Shanxi Province People’s Hospital, ( https://ror.org/009czp143) Taiyuan, 030012 Shanxi China
                [4 ]Department of blood transfusion, Shanxi Provincial People’s Hospital, ( https://ror.org/009czp143) Taiyuan, 030032 Shanxi China
                [5 ]Department of central laboratory, Shanxi Provincial People’s Hospital, ( https://ror.org/009czp143) Taiyuan, 030032 Shanxi China
                Article
                3130
                10.1186/s12935-023-03130-2
                10693166
                38041196
                c5f0e6be-c0a3-432d-b332-ffc2a8981bb8
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 30 August 2023
                : 9 November 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006407, Natural Science Foundation of Henan Province;
                Award ID: 232300420283
                Funded by: Scientific Research Start-up Foundation for Doctor of Zhoukou Normal University
                Award ID: ZKNUC2020019
                Funded by: Henan Science and Technology Research Plan Project of China
                Award ID: 222102110412
                Funded by: General Youth Project of Shanxi Natural Science Foundation
                Award ID: 201901D211523
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2023

                Oncology & Radiotherapy
                cancer stem cells,csc niche,cellular components,extracellular matrix,therapeutic strategies

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