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The Hallmarks of Cancer Stem Cells
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The Hallmarks of Cancer Stem Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 March 2025 | Viewed by 8153

Special Issue Editors

Prof. Dr. Geoffrey Brown

E-Mail Website
Guest Editor
School of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Interests: the use of synthetic retinoids and vitamins D as drug substances; cancer and normal stem cells; anticancer therapies; blood cell development; abnormalities in cancer stem cells
Special Issues, Collections and Topics in MDPI journals
Dr. Maarten Hoogenkamp

E-Mail Website
Guest Editor
Insitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Interests: cell differentiation; chromatin organisation; transcription factor interplay; carcinogenesis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ewa Marcinkowska

E-Mail Website
Guest Editor
Department of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland
Interests: vitamin D; vitamin D analogs; retinoids; semi-selective activities; cell differentiation; nuclear receptors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

From the very beginning of efforts employed to develop a cure for cancer, the overarching principle has been to target characteristics that are specific to cancer cells so as to spare normal cells as much as possible. In 2011, Hanahan and Weinberg published their landmark review article entitled “Hallmarks of cancer: the next generation”. Traits that were linked to the abnormal behaviour of cancer cells included the controls pertaining to viability, proliferation, differentiation, cytostasis, and motility. Additionally, the longstanding use of chemotherapeutics and radiotherapy to treat cancer has targeted proliferating cells. In 2008, Dick brought to attention how stem cell concepts had renewed cancer research. Cancer stem cells and, as first described, the leukaemia stem cells for acute myeloid leukaemia are rare cells (<0.1%) that sustain a malignancy. Like normal stem cells, cancer stem cells generate a hierarchy of cells, but the offspring are abnormal. Cancer stem cells are spared by conventional chemotherapy and appear to be the prime cause of disease relapse and metastasis; therefore, for the past 10 years, substantial efforts have been employed to target these cells.

Differences between normal and cancer stem cells are important to targeting cancer stem cells. This Special Issue welcomes articles on various aspects to normal stem cells versus cancer stem cells as follows.

Prof. Dr. Geoffrey Brown
Dr. Maarten Hoogenkamp
Prof. Dr. Ewa Marcinkowska
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • developmental biology of normal and cancer stem cells
  • other differences to cell status, for example, survivability and quiescence versus proliferation
  • metabolic differences
  • intracellular signalling
  • surface marker expression
  • global gene expression including microRNAs
  • the frequency of cancer stem cells within a tumour
  • importance of cancer stem cells to disease relapse
  • importance of cancer stem cells to disease metastasis
  • agents that target cancer stem cells

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Published Papers (3 papers)

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Research

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17 pages, 5198 KiB  
Article
Involvement of Mitochondria in the Selective Response to Microsecond Pulsed Electric Fields on Healthy and Cancer Stem Cells in the Brain
by Arianna Casciati, Anna Rita Taddei, Elena Rampazzo, Luca Persano, Giampietro Viola, Alice Cani, Silvia Bresolin, Vincenzo Cesi, Francesca Antonelli, Mariateresa Mancuso, Caterina Merla and Mirella Tanori
Int. J. Mol. Sci. 2024, 25(4), 2233; https://doi.org/10.3390/ijms25042233 - 13 Feb 2024
Viewed by 1570
Abstract
In the last few years, pulsed electric fields have emerged as promising clinical tools for tumor treatments. This study highlights the distinct impact of a specific pulsed electric field protocol, PEF-5 (0.3 MV/m, 40 μs, 5 pulses), on astrocytes (NHA) and medulloblastoma (D283) [...] Read more.
In the last few years, pulsed electric fields have emerged as promising clinical tools for tumor treatments. This study highlights the distinct impact of a specific pulsed electric field protocol, PEF-5 (0.3 MV/m, 40 μs, 5 pulses), on astrocytes (NHA) and medulloblastoma (D283) and glioblastoma (U87 NS) cancer stem-like cells (CSCs). We pursued this goal by performing ultrastructural analyses corroborated by molecular/omics approaches to understand the vulnerability or resistance mechanisms triggered by PEF-5 exposure in the different cell types. Electron microscopic analyses showed that, independently of exposed cells, the main targets of PEF-5 were the cell membrane and the cytoskeleton, causing membrane filopodium-like protrusion disappearance on the cell surface, here observed for the first time, accompanied by rapid cell swelling. PEF-5 induced different modifications in cell mitochondria. A complete mitochondrial dysfunction was demonstrated in D283, while a mild or negligible perturbation was observed in mitochondria of U87 NS cells and NHAs, respectively, not sufficient to impair their cell functions. Altogether, these results suggest the possibility of using PEF-based technology as a novel strategy to target selectively mitochondria of brain CSCs, preserving healthy cells. Full article
(This article belongs to the Special Issue The Hallmarks of Cancer Stem Cells)
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Review

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69 pages, 2437 KiB  
Review
Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways
by Maya R. MacLean, Olivia L. Walker, Raj Pranap Arun, Wasundara Fernando and Paola Marcato
Int. J. Mol. Sci. 2024, 25(7), 4102; https://doi.org/10.3390/ijms25074102 - 7 Apr 2024
Cited by 4 | Viewed by 3623
Abstract
Cancer stem cells (CSCs) represent a subpopulation within tumors that promote cancer progression, metastasis, and recurrence due to their self-renewal capacity and resistance to conventional therapies. CSC-specific markers and signaling pathways highly active in CSCs have emerged as a promising strategy for improving [...] Read more.
Cancer stem cells (CSCs) represent a subpopulation within tumors that promote cancer progression, metastasis, and recurrence due to their self-renewal capacity and resistance to conventional therapies. CSC-specific markers and signaling pathways highly active in CSCs have emerged as a promising strategy for improving patient outcomes. This review provides a comprehensive overview of the therapeutic targets associated with CSCs of solid tumors across various cancer types, including key molecular markers aldehyde dehydrogenases, CD44, epithelial cellular adhesion molecule, and CD133 and signaling pathways such as Wnt/β-catenin, Notch, and Sonic Hedgehog. We discuss a wide array of therapeutic modalities ranging from targeted antibodies, small molecule inhibitors, and near-infrared photoimmunotherapy to advanced genetic approaches like RNA interference, CRISPR/Cas9 technology, aptamers, antisense oligonucleotides, chimeric antigen receptor (CAR) T cells, CAR natural killer cells, bispecific T cell engagers, immunotoxins, drug-antibody conjugates, therapeutic peptides, and dendritic cell vaccines. This review spans developments from preclinical investigations to ongoing clinical trials, highlighting the innovative targeting strategies that have been informed by CSC-associated pathways and molecules to overcome therapeutic resistance. We aim to provide insights into the potential of these therapies to revolutionize cancer treatment, underscoring the critical need for a multi-faceted approach in the battle against cancer. This comprehensive analysis demonstrates how advances made in the CSC field have informed significant developments in novel targeted therapeutic approaches, with the ultimate goal of achieving more effective and durable responses in cancer patients. Full article
(This article belongs to the Special Issue The Hallmarks of Cancer Stem Cells)
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38 pages, 5307 KiB  
Review
Cancer Stem Cells from Definition to Detection and Targeted Drugs
by Barbara Ruszkowska-Ciastek, Katarzyna Kwiatkowska, Dorinda Marques-da-Silva and Ricardo Lagoa
Int. J. Mol. Sci. 2024, 25(7), 3903; https://doi.org/10.3390/ijms25073903 - 31 Mar 2024
Cited by 1 | Viewed by 1877
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue The Hallmarks of Cancer Stem Cells)
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