Cancer Stem Cells and Targeted Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 9980

Special Issue Editor

Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia
Interests: cancer biology and cancer therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

New scientific evidence is increasingly proving that cancer stem cells (or tumor-initiating cells) play a vital role in tumor initiation, development, progress and metastasis. They are also responsible for tumor recurrence and drug resistance. In addition, it is believed that they represent the origin of tumor heterogenicity. Therefore, they are an ideal target for cancer therapy and can eventually lead to the discovery of a cure.

However, CSCs are few in number and lack unique surface markers to identify them, making targeted therapy difficult. Studies on CSCs to gain a greater understanding of their biological activity and behavior in order to identify therapeutic targets are very important. The new methods related to these topics and the attempt to isolate and culture CSCs, especially concerning the methods that retain their stem properties and the subjects of proper animal models as well as organoids, are also critical for our ever-increasing understanding of CSC biology and developing CSC-targeted therapies.

This Special Issue aims to publish/collect research on CSC biology and related therapies targeting CSCs, including establishing in vitro or in vivo studies and organoid models).

Original research articles and reviews are invited for submission for the current Special Issue. Research areas may include (but are not limited to) the following: cancer stem cell biology (origin, development, distribution, migration, self-renewal, and differentiation); identification of biomarkers or therapeutic targets of CSCs (surface markers, signaling pathways, and gene markers); targeted therapies (with any drugs, such as chemo drugs, natural products, pathway inhibitors, and their delivery systems using nanotechnology).

I look forward to receiving your contributions.

Dr. Wenyi Gu
Guest Editor

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Keywords

  • tumor initiation
  • tumor colonization
  • biomarkers for cancer stem cells
  • signaling pathways for cancer stem cells
  • cancer differentiation and self-renewal
  • cancer therapy targeting cancer stem cells
  • drug delivery targeting cancer stem cells
  • TME targeted therapy
  • hypoxia targeted cancer therapy
  • self-renewal targeted cancer therapy

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Published Papers (3 papers)

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Research

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18 pages, 6104 KiB  
Article
Suppression of Cancer Cell Stemness and Drug Resistance via MYC Destabilization by Deubiquitinase USP45 Inhibition with a Natural Small Molecule
by Xiao Tu, Chuncheng Li, Wen Sun, Xi Tian, Qiufu Li, Shaoxin Wang, Xiaoling Ding and Zhen Huang
Cancers 2023, 15(3), 930; https://doi.org/10.3390/cancers15030930 - 1 Feb 2023
Cited by 8 | Viewed by 2889
Abstract
Cancer stem cells (CSCs) play significant roles in cancer development, drug resistance and cancer recurrence. In cancer treatments based on the CSC characteristics and inducing factors, MYC is a promising target for therapeutic molecules. Although it has been regarded as an undrugable target, [...] Read more.
Cancer stem cells (CSCs) play significant roles in cancer development, drug resistance and cancer recurrence. In cancer treatments based on the CSC characteristics and inducing factors, MYC is a promising target for therapeutic molecules. Although it has been regarded as an undrugable target, its stability tightly regulated by the ubiquitin–proteasome system offers a new direction for molecule targeting and cancer treatment. Herein we report our discoveries in this research area, and we have found that deubiquitinase USP45 can directly bind with MYC, resulting in its deubiquitination and stabilization. Further, USP45 overexpressing can upregulate MYC, and this overexpressing can significantly enhance cancer development, cancer cell stemness and drug resistance. Interestingly, without enhancing cancer development, MYC silencing with shRNA can only suppress USP45-induced stemness and drug resistance. Moreover, we have identified that USP45 can be specifically bound and inhibited by a natural small molecule (α-mangostin), in turn significantly suppressing USP45-induced stemness and drug resistance. Since USP45 is significantly expressed in cervical tumors, we have discovered that the combination of α-mangostin and doxorubicin can significantly inhibit USP45-induced cervical tumorigenesis in an animal model. In general, on the basis of our USP45 discoveries on its MYC deubiquitination and α-mangostin inhibition, suppressing USP45 has opened a new window for suppressing cancer development, stemness and drug resistance. Full article
(This article belongs to the Special Issue Cancer Stem Cells and Targeted Therapy)
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16 pages, 2691 KiB  
Article
RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells
by Yushu Gu, Valentin Bobrin, Dayong Zhang, Bing Sun, Chun Ki Ng, Sung-Po R. Chen, Wenyi Gu and Michael J. Monteiro
Cancers 2023, 15(1), 234; https://doi.org/10.3390/cancers15010234 - 30 Dec 2022
Cited by 4 | Viewed by 2181
Abstract
Cancer stem cells (CSCs) are primarily responsible for tumour drug resistance and metastasis; thus, targeting CSCs can be a promising approach to stop cancer recurrence. However, CSCs are small in numbers and readily differentiate into matured cancer cells, making the study of their [...] Read more.
Cancer stem cells (CSCs) are primarily responsible for tumour drug resistance and metastasis; thus, targeting CSCs can be a promising approach to stop cancer recurrence. However, CSCs are small in numbers and readily differentiate into matured cancer cells, making the study of their biological features, including therapeutic targets, difficult. The use of three-dimensional (3D) culture systems to enrich CSCs has some limitations, including low sphere forming efficiency, enzymatic digestion that may damage surface proteins, and more importantly no means to sustain the stem properties. A responsive 3D polymer extracellular matrix (ECM) system coated with RGD was used to enrich CSCs, sustain stemness and avoid enzymatic dissociation. RGD was used as a targeting motif and a ligand to bind integrin receptors. We found that the system was able to increase sphere forming efficiency, promote the growth of spheric cells, and maintain stemness-associated properties compared to the current 3D culture. We showed that continuous culture for three generations of colon tumour spheroid led to the stem marker CD24 gradually increasing. Furthermore, the new system could enhance the cancer cell sphere forming ability for the difficult triple negative breast cancer cells, MBA-MD-231. The key stem gene expression for colon cancer also increased with the new system. Further studies indicated that the concentration of RGD, especially at high doses, could inhibit stemness. Taken together, our data demonstrate that our RGD-based ECM system can facilitate the enrichment of CSCs and now allow for the investigation of new therapeutic approaches for colorectal cancer or other cancers. Full article
(This article belongs to the Special Issue Cancer Stem Cells and Targeted Therapy)
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Review

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35 pages, 1829 KiB  
Review
Immunotargeting of Cancer Stem Cells
by Ayse Sedef Köseer, Simona Di Gaetano, Claudia Arndt, Michael Bachmann and Anna Dubrovska
Cancers 2023, 15(5), 1608; https://doi.org/10.3390/cancers15051608 - 5 Mar 2023
Cited by 6 | Viewed by 4195
Abstract
The generally accepted view is that CSCs hijack the signaling pathways attributed to normal stem cells that regulate the self-renewal and differentiation processes. Therefore, the development of selective targeting strategies for CSC, although clinically meaningful, is associated with significant challenges because CSC and [...] Read more.
The generally accepted view is that CSCs hijack the signaling pathways attributed to normal stem cells that regulate the self-renewal and differentiation processes. Therefore, the development of selective targeting strategies for CSC, although clinically meaningful, is associated with significant challenges because CSC and normal stem cells share many important signaling mechanisms for their maintenance and survival. Furthermore, the efficacy of this therapy is opposed by tumor heterogeneity and CSC plasticity. While there have been considerable efforts to target CSC populations by the chemical inhibition of the developmental pathways such as Notch, Hedgehog (Hh), and Wnt/β-catenin, noticeably fewer attempts were focused on the stimulation of the immune response by CSC-specific antigens, including cell-surface targets. Cancer immunotherapies are based on triggering the anti-tumor immune response by specific activation and targeted redirecting of immune cells toward tumor cells. This review is focused on CSC-directed immunotherapeutic approaches such as bispecific antibodies and antibody-drug candidates, CSC-targeted cellular immunotherapies, and immune-based vaccines. We discuss the strategies to improve the safety and efficacy of the different immunotherapeutic approaches and describe the current state of their clinical development. Full article
(This article belongs to the Special Issue Cancer Stem Cells and Targeted Therapy)
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