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Cancer Stem Cells from Definition to Detection and Targeted Drugs. Int. J. Mol. Sci. 2024, 25, 3903 . [https://doi.org/10.3390/ijms25073903](https://doi.org/10.3390/ijms25073903)  \nAcademic Editors: Geoffrey Brown, Ewa Marcinkowska and Maarten Hoogenkamp  \nReceived: 26 February 2024  \nRevised: 28 March 2024  \nAccepted: 29 March 2024  \nPublished: 31 March 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University, Collegium Medicum, 85-094 Bydgoszcz, Poland  \n2 Department of Laboratory Diagnostics, Jan Biziel University Hospital No. 2, 85-168 Bydgoszcz, Poland; [katarzynakwiatkowska@abs.umk.pl](katarzynakwiatkowska@abs.umk.pl)  \n3 Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials (LSRE-LCM), Polytechnic Institute of Leiria, 2411-901 Leiria, Portugal; [dorinda.silva@ipleiria.pt](dorinda.silva@ipleiria.pt) (D.M.-d.-S.); [ricardo.lagoa@ipleiria.pt](ricardo.lagoa@ipleiria.pt) (R.L.)  \n4 Associate Laboratory in Chemical Engineering (ALiCE), Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal  \n5 School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena-Alto do Vieiro, 2411-901 Leiria, Portugal  \n* Correspondence: [ruszkowska.basia@gmail.com](ruszkowska.basia@gmail.com)  \nAbstract: Cancers remain the second leading cause of mortality in the world. Preclinical and clinical studies point an important role of cancer/leukaemia stem cells (CSCs/LSCs) in the colonisation at secondary organ sites upon metastatic spreading, although the precise mechanisms for specific actions are still not fully understood. Reviewing the present knowledge on the crucial role of CSCs/LSCs, their plasticity, and population heterogeneity in treatment failures in cancer patients is timely. Standard chemotherapy, which acts mainly on rapidly dividing cells, is unable to adequately affect CSCs with a low proliferation rate. One of the proposed mechanisms of CSC resistance to anticancer agents is the fact that these cells can easily shift between different phases of the cell cycle in response to typical cell stimuli induced by anticancer drugs. In this work, we reviewed the recent studies on CSC/LSC alterations associated with disease recurrence, and we systematised the functional assays, markers, and novel methods for CSCs screening. This review emphasises CSCs’involvement in cancer progression and metastasis, as well as CSC/LSC targeting by synthetic and natural compounds aiming at their elimination or modulation of stemness properties.  \nKeywords: cancer stem cells; leukaemia stem cells; cancer progression; solid tumours; haematological malignancies; tumour microenvironment; artificial intelligence; targeted therapy; polyphenols  \n1. Introduction  \nDespite extensive research into the nature of cancers, they remain a leading cause of death. Based on the GLOBOCAN 2020 registry with over 10 million fatal events in 2020 alone, including lung cancer (1,796,144), colorectal (935,173), liver (830,180), stomach (768,793), breast (684,996), oesophagus (544,076), pancreas (466,003), prostate (375,304), cervix uteri (341,831), leukaemia (311,594), and so on [1] . Thus, many questions are still to be answered in this regard: What else do we need to know to tame cancers? Have we reached the glass ceiling in this rega","cbCaiiFb6yVzTYv9","https://ap.wps.com/l/cbCaiiFb6yVzTYv9","pdf",5434465,35,"English","# Introduction\n## Cancer stem cells in cancer biology\n# Review scope and focus\n## Functional assays, markers, and screening methods\n## Targeting strategies with synthetic and natural compounds","[{\"question\":\"Why are cancer stem cells considered central to cancer progression and metastasis?\",\"answer\":\"Cancer stem cells (CSCs/LSCs) support tumour initiation and colonisation, show pro-metastatic and pro-recurrence potential, and exhibit low drug sensitivity. They can maintain tumour-initiating environments and influence growth and spreading.\"},{\"question\":\"What limits standard chemotherapy against cancer stem cells?\",\"answer\":\"Standard chemotherapy primarily acts on rapidly dividing cells, while CSCs often have low proliferation rates. This makes CSCs less responsive to conventional treatment approaches.\"},{\"question\":\"How does this review structure its coverage of CSC research?\",\"answer\":\"The review summarizes recent studies on CSC/LSC alterations associated with recurrence and systematizes functional assays, markers, and novel methods used for CSC screening.\"}]","Cancer Stem Cells from Definition to Detection and Targeted Drugs | PDF",1789977154,88]