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Cells
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CSCs Identification and Targeting Therapies: Advances and Challenges
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CSCs Identification and Targeting Therapies: Advances and Challenges

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (15 July 2019) | Viewed by 23836

Special Issue Editors

Dr. Tarik Regad

E-Mail Website
Guest Editor
John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, UK
Interests: cancer stem cells (CSCs); CSCs’ specific biomarkers; CSCs’ targeting therapies; epithelial–mesenchymal transition; cancer invasion and metastasis
Prof. Dr. Gianpaolo Papaccio

E-Mail Website
Guest Editor
Department of Experimental Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Via Armanni, 5, Naples, Italy
Interests: stem cells; cancer stem cells; cancer stem cells identification and eradication; bone; remodeling; sarcomas; adipose stem cells; differentiation; head and neck cancer

Special Issue Information

Dear Colleagues,

Chemoresistance is a major problem in cancer therapy, as aggressive cancer cells develop mechanisms to counteract chemotherapeutic drugs. Cancer stem cells (CSCs) are considered to be at the origin of cancer relapse and recurrence in cancer patients and following chemotherapy. Like their stem cell counterparts, CSCs possess the stemness properties of self-renewal and the ability to generate differentiated cells that contribute to tumor heterogeneity. Although several CSC biomarkers have been identified, the specificity of their expression remains a concern. Therefore, the identification of specific CSC biomarkers and associated cellular pathways for targeted cancer therapies is a major challenge facing scientists and clinicians working in this moving field. This issue will focus on refining recent advances in our understanding of CSCs’ role in chemoresistance and cancer progression, and determine available therapeutic strategies to target these highly malignant cells.

Dr. Tarik Regad
Prof. Gianpaolo Papaccio
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. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • Cancer stem cells
  • Invasion
  • Metastasis
  • Chemoresistance
  • Epithelial–mesenchymal transition
  • Biomarkers
  • CSC-targeting therapies

Published Papers (3 papers)

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Research

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20 pages, 6946 KiB  
Article
Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma
by Vithushiya Yoganandarajah, Josie Patel, Bede van Schaijik, Nicholas Bockett, Helen D. Brasch, Erin Paterson, Dalice Sim, Paul F. Davis, Imogen M. Roth, Tinte Itinteang and Swee T. Tan
Cells 2020, 9(2), 324; https://doi.org/10.3390/cells9020324 - 30 Jan 2020
Cited by 19 | Viewed by 3785
Abstract
Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM [...] Read more.
Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4, and c-MYC in all samples, while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n = 6) and reverse-transcription quantitative polymerase chain reaction (n = 5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer. Full article
(This article belongs to the Special Issue CSCs Identification and Targeting Therapies: Advances and Challenges)
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Review

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19 pages, 927 KiB  
Review
Cancer Stem Cells and Targeting Strategies
by Luisa Barbato, Marco Bocchetti, Anna Di Biase and Tarik Regad
Cells 2019, 8(8), 926; https://doi.org/10.3390/cells8080926 - 18 Aug 2019
Cited by 125 | Viewed by 7863
Abstract
Chemoresistance is a major problem in cancer therapy as cancer cells develop mechanisms that counteract the effect of chemotherapeutic compounds, leading to relapse and the development of more aggressive cancers that contribute to poor prognosis and survival rates of treated patients. Cancer stem [...] Read more.
Chemoresistance is a major problem in cancer therapy as cancer cells develop mechanisms that counteract the effect of chemotherapeutic compounds, leading to relapse and the development of more aggressive cancers that contribute to poor prognosis and survival rates of treated patients. Cancer stem cells (CSCs) play a key role in this event. Apart from their slow proliferative property, CSCs have developed a range of cellular processes that involve drug efflux, drug enzymatic inactivation and other mechanisms. In addition, the microenvironment where CSCs evolve (CSC niche), effectively contributes to their role in cancer initiation, progression and chemoresistance. In the CSC niche, immune cells, mesenchymal stem cells (MSCs), endothelial cells and cancer associated fibroblasts (CAFs) contribute to the maintenance of CSC malignancy via the secretion of factors that promote cancer progression and resistance to chemotherapy. Due to these factors that hinder successful cancer therapies, CSCs are a subject of intense research that aims at better understanding of CSC behaviour and at developing efficient targeting therapies. In this review, we provide an overview of cancer stem cells, their role in cancer initiation, progression and chemoresistance, and discuss the progress that has been made in the development of CSC targeted therapies. Full article
(This article belongs to the Special Issue CSCs Identification and Targeting Therapies: Advances and Challenges)
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33 pages, 1665 KiB  
Review
Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies
by Abdul Q. Khan, Eiman I. Ahmed, Noor R. Elareer, Kulsoom Junejo, Martin Steinhoff and Shahab Uddin
Cells 2019, 8(8), 840; https://doi.org/10.3390/cells8080840 - 05 Aug 2019
Cited by 194 | Viewed by 11665
Abstract
Recent biomedical discoveries have revolutionized the concept and understanding of carcinogenesis, a complex and multistep phenomenon which involves accretion of genetic, epigenetic, biochemical, and histological changes, with special reference to MicroRNAs (miRNAs) and cancer stem cells (CSCs). miRNAs are small noncoding molecules known [...] Read more.
Recent biomedical discoveries have revolutionized the concept and understanding of carcinogenesis, a complex and multistep phenomenon which involves accretion of genetic, epigenetic, biochemical, and histological changes, with special reference to MicroRNAs (miRNAs) and cancer stem cells (CSCs). miRNAs are small noncoding molecules known to regulate expression of more than 60% of the human genes, and their aberrant expression has been associated with the pathogenesis of human cancers and the regulation of stemness features of CSCs. CSCs are the small population of cells present in human malignancies well-known for cancer resistance, relapse, tumorigenesis, and poor clinical outcome which compels the development of novel and effective therapeutic protocols for better clinical outcome. Interestingly, the role of miRNAs in maintaining and regulating the functioning of CSCs through targeting various oncogenic signaling pathways, such as Notch, wingless (WNT)/β-Catenin, janus kinases/ signal transducer and activator of transcription (JAK/STAT), phosphatidylinositol 3-kinase/ protein kinase B (PI3/AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-kB), is critical and poses a huge challenge to cancer treatment. Based on recent findings, here, we have documented the regulatory action or the underlying mechanisms of how miRNAs affect the signaling pathways attributed to stemness features of CSCs, such as self-renewal, differentiation, epithelial to mesenchymal transition (EMT), metastasis, resistance and recurrence etc., associated with the pathogenesis of various types of human malignancies including colorectal cancer, lung cancer, breast cancer, head and neck cancer, prostate cancer, liver cancer, etc. We also shed light on the fact that the targeted attenuation of deregulated functioning of miRNA related to stemness in human carcinogenesis could be a viable approach for cancer treatment. Full article
(This article belongs to the Special Issue CSCs Identification and Targeting Therapies: Advances and Challenges)
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