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Mechanisms of Anticancer Therapy Resistance: The Role 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: closed (31 July 2021) | Viewed by 15942

Special Issue Editor

Dr. Julhash U. Kazi

E-Mail Website
Guest Editor
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, 22381 Lund, Sweden
Interests: anticancer drugs resistance; drug repurposing; molecular targeted therapy; predictive markers; receptor tyrosine kinase biology; cellular signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A Special Issue on the topic "Mechanisms of Anticancer Therapy Resistance: The Role of Cancer Stem Cells" is being prepared for the journal IJMS. Despite incredible progress in cancer treatment, the cure rate remains quite low due to the fact that almost all cancer patients develop resistance to anticancer therapies. Cancer treatment elicits specific genetic and epigenetic changes in cancer cells and in the microenvironment in which cancer cells reside, contributing to resistance. Accumulating pieces of evidence suggest that a small subpopulation of cancer cells known as cancer stem cells derive therapy resistance and thereby cancer relapse. The field is moving forward rapidly, and gaining a better understanding of the features of cancer stem cells is important to establish the foundation of efficient new cancer treatments.

Original manuscripts and reviews dealing with therapy resistance issues in cancer and focusing on the cancer stem cells are very welcome from experts of the field.

Dr. Julhash U. Kazi
Guest Editor

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

  • drug resistance
  • anticancer therapy
  • cancer stem cells
  • targeted therapy

Published Papers (5 papers)

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Editorial

Jump to: Research, Review

4 pages, 359 KiB  
Editorial
Mechanisms of Anticancer Therapy Resistance: The Role of Cancer Stem Cells
by Julhash U. Kazi
Int. J. Mol. Sci. 2020, 21(23), 9006; https://doi.org/10.3390/ijms21239006 - 27 Nov 2020
Cited by 7 | Viewed by 1869
Abstract
Despite incredible progress in anticancer therapy development, resistance to therapy is the major factor limiting the cure of cancer patients [...] Full article
(This article belongs to the Special Issue Mechanisms of Anticancer Therapy Resistance: The Role of Cancer Stem Cells)
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Research

Jump to: Editorial, Review

14 pages, 3475 KiB  
Article
Radiotherapy-Resistant Breast Cancer Cells Enhance Tumor Progression by Enhancing Premetastatic Niche Formation through the HIF-1α-LOX Axis
by Young Shin Ko, Trojan Rugira, Hana Jin, Young Nak Joo and Hye Jung Kim
Int. J. Mol. Sci. 2020, 21(21), 8027; https://doi.org/10.3390/ijms21218027 - 28 Oct 2020
Cited by 11 | Viewed by 2784
Abstract
Cancer stem cells (CSCs) exist in solid tumors and contribute to therapeutic resistance and disease recurrence. Previously, we reported that radiotherapy-resistant (RT-R)-MDA-MB-231 cells from highly metastatic MDA-MB-231 cells produced more CSCs than any other RT-R-breast cancer cells and showed therapeutic resistance and enhanced [...] Read more.
Cancer stem cells (CSCs) exist in solid tumors and contribute to therapeutic resistance and disease recurrence. Previously, we reported that radiotherapy-resistant (RT-R)-MDA-MB-231 cells from highly metastatic MDA-MB-231 cells produced more CSCs than any other RT-R-breast cancer cells and showed therapeutic resistance and enhanced invasiveness. Hypoxia inducible factor-1α (HIF-1α) induced in the tumor microenvironment leads to the release of lysyl oxidase (LOX), which mediates collagen crosslinking at distant sites to facilitate environmental changes that allow cancer cells to easily metastasize. Therefore, in this study, we investigated whether RT-R-MDA-MB-231 cells induce greater HIF-1α expression, LOX secretion, and premetastatic niche formation than MDA-MB-231 cells do. RT-R-MDA-MB-231 cells increased HIF-1α expression and LOX secretion compared with MDA-MB-231 cells. Mice harboring RT-R-MDA-MB-231 cell xenografts showed enhanced tumor growth and higher expression of the CSC markers, CD44, Notch-4, and Oct3/4. In addition, mice injected with RT-R-MDA-MB-231 cells exhibited a higher level of HIF-1α in tumor tissue, increased secretion of LOX in plasma, higher induced levels of crosslinked collagen, and a higher population of CD11b+ BMDC recruitment around lung tissue, compared with those injected with MDA-MB-231 cells. These results suggest that RT-R-MDA-MB-231 cells contribute to tumor progression by enhancing premetastatic niche formation through the HIF-1α-LOX axis. Full article
(This article belongs to the Special Issue Mechanisms of Anticancer Therapy Resistance: The Role of Cancer Stem Cells)
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Review

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17 pages, 1216 KiB  
Review
Therapeutic Strategies for Targeting Ovarian Cancer Stem Cells
by Wookyeom Yang, Dasol Kim, Dae Kyoung Kim, Kyung Un Choi, Dong Soo Suh and Jae Ho Kim
Int. J. Mol. Sci. 2021, 22(10), 5059; https://doi.org/10.3390/ijms22105059 - 11 May 2021
Cited by 20 | Viewed by 3511
Abstract
Ovarian cancer is a fatal gynecological malignancy. Although first-line chemotherapy and surgical operation are effective treatments for ovarian cancer, its clinical management remains a challenge owing to intrinsic or acquired drug resistance and relapse at local or distal lesions. Cancer stem cells (CSCs) [...] Read more.
Ovarian cancer is a fatal gynecological malignancy. Although first-line chemotherapy and surgical operation are effective treatments for ovarian cancer, its clinical management remains a challenge owing to intrinsic or acquired drug resistance and relapse at local or distal lesions. Cancer stem cells (CSCs) are a small subpopulation of cells inside tumor tissues, and they can self-renew and differentiate. CSCs are responsible for the cancer malignancy involved in relapses as well as resistance to chemotherapy and radiation. These malignant properties of CSCs are regulated by cell surface receptors and intracellular pluripotency-associated factors triggered by internal or external stimuli from the tumor microenvironment. The malignancy of CSCs can be attenuated by individual or combined restraining of cell surface receptors and intracellular pluripotency-associated factors. Therefore, targeted therapy against CSCs is a feasible therapeutic tool against ovarian cancer. In this paper, we review the prominent roles of cell surface receptors and intracellular pluripotency-associated factors in mediating the stemness and malignancy of ovarian CSCs. Full article
(This article belongs to the Special Issue Mechanisms of Anticancer Therapy Resistance: The Role of Cancer Stem Cells)
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20 pages, 1178 KiB  
Review
Pancreatic Cancer and Therapy: Role and Regulation of Cancer Stem Cells
by Susmita Barman, Iram Fatima, Amar B. Singh and Punita Dhawan
Int. J. Mol. Sci. 2021, 22(9), 4765; https://doi.org/10.3390/ijms22094765 - 30 Apr 2021
Cited by 24 | Viewed by 4131
Abstract
Despite significant improvements in clinical management, pancreatic cancer (PC) remains one of the deadliest cancer types, as it is prone to late detection with extreme metastatic properties. The recent findings that pancreatic cancer stem cells (PaCSCs) contribute to the tumorigenesis, progression, and chemoresistance [...] Read more.
Despite significant improvements in clinical management, pancreatic cancer (PC) remains one of the deadliest cancer types, as it is prone to late detection with extreme metastatic properties. The recent findings that pancreatic cancer stem cells (PaCSCs) contribute to the tumorigenesis, progression, and chemoresistance have offered significant insight into the cancer malignancy and development of precise therapies. However, the heterogeneity of cancer and signaling pathways that regulate PC have posed limitations in the effective targeting of the PaCSCs. In this regard, the role for K-RAS, TP53, Transforming Growth Factor-β, hedgehog, Wnt and Notch and other signaling pathways in PC progression is well documented. In this review, we discuss the role of PaCSCs, the underlying molecular and signaling pathways that help promote pancreatic cancer development and metastasis with a specific focus on the regulation of PaCSCs. We also discuss the therapeutic approaches that target different PaCSCs, intricate mechanisms, and therapeutic opportunities to eliminate heterogeneous PaCSCs populations in pancreatic cancer. Full article
(This article belongs to the Special Issue Mechanisms of Anticancer Therapy Resistance: The Role of Cancer Stem Cells)
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18 pages, 685 KiB  
Review
Roles of microRNAs in Gastrointestinal Cancer Stem Cell Resistance and Therapeutic Development
by Ga-Ram Hwang, John G. Yuen and Jingfang Ju
Int. J. Mol. Sci. 2021, 22(4), 1624; https://doi.org/10.3390/ijms22041624 - 5 Feb 2021
Cited by 10 | Viewed by 2954
Abstract
Resistance to cancer treatment is one of the major challenges currently faced when treating gastrointestinal (GI) cancers. A major contributing factor to this resistance is the presence of cancer stem cells (CSCs) in GI cancers (e.g., colorectal, pancreatic, gastric, liver cancer). Non-coding RNAs, [...] Read more.
Resistance to cancer treatment is one of the major challenges currently faced when treating gastrointestinal (GI) cancers. A major contributing factor to this resistance is the presence of cancer stem cells (CSCs) in GI cancers (e.g., colorectal, pancreatic, gastric, liver cancer). Non-coding RNAs, such as microRNAs (miRNAs), have been found to regulate several key targets that are responsible for cancer stemness, and function as oncogenic miRNAs (oncomiRs) or tumor suppressor miRNAs. As a result, several miRNAs have been found to alter, or be altered by, the expression of CSC-defining markers and their related pathways. These miRNAs can be utilized to affect stemness in multiple ways, including directly targeting CSCs and enhancing the efficacy of cancer therapeutics. This review highlights current studies regarding the roles of miRNAs in GI CSCs, and efforts towards the development of cancer therapeutics. Full article
(This article belongs to the Special Issue Mechanisms of Anticancer Therapy Resistance: The Role of Cancer Stem Cells)
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