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Cells
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Cancer Stem-Like Cells and Cancer Therapeutic Strategy
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Cancer Stem-Like Cells and Cancer Therapeutic Strategy

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

Deadline for manuscript submissions: closed (23 April 2023) | Viewed by 14092

Special Issue Editor

Prof. Dr. Liwu Fu

E-Mail Website
Guest Editor
Department of Experimental Research (Cancer Institute), Cancer Center, Sun Yat-sen University, Guangzhou 510060, China
Interests: multidrug resistance; tyrosine kinase inhibitor; ABC transporters; exosomes; cancer; cancer stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer stem-like cells are the main causes of carcinogenesis, recurrence, metastasis, and drug resistance. Killing tumor stem cells is expected to cure patients with cancer. Although the concept of tumor stem cells was proposed 40 years ago, the key signaling molecules of cancer stem cell evolution remain unclear. With many scientists working on the key regulatory molecules of the malignant evolution of stem cells and the treatment of targeted cancer stem cells, this Special Issue hopes to publish your achievements in this field while at the same time improving the academic reputation of Cells.

Prof. Dr. Liwu Fu
Guest Editor

Manuscript Submission Information

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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
  • stemness
  • stem cells
  • EMT
  • dormancy
  • targeted therapy
  • drug resistance

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Published Papers (4 papers)

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Research

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14 pages, 4414 KiB  
Article
Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids
by Dongil Park, Dahye Lee, Yoonjoo Kim, Yeonhee Park, Yeon-Jae Lee, Jeong Eun Lee, Min-Kyung Yeo, Min-Woong Kang, Yooyoung Chong, Sung Joon Han, Jinwook Choi, Jong-Eun Park, Yongjun Koh, Jaehyeok Lee, YongKeun Park, Ryul Kim, Jeong Seok Lee, Jimin Choi, Sang-Hyun Lee, Bosung Ku, Da Hyun Kang and Chaeuk Chungadd Show full author list remove Hide full author list
Cells 2023, 12(14), 1854; https://doi.org/10.3390/cells12141854 - 14 Jul 2023
Cited by 12 | Viewed by 4853
Abstract
One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent [...] Read more.
One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer. Full article
(This article belongs to the Special Issue Cancer Stem-Like Cells and Cancer Therapeutic Strategy)
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12 pages, 1783 KiB  
Article
The Antiepileptic Drug Oxcarbazepine Inhibits the Growth of Patient-Derived Isocitrate Dehydrogenase Mutant Glioma Stem-like Cells
by Philip Dao Trong, Gerhard Jungwirth, Andreas Unterberg, Christel Herold-Mende and Rolf Warta
Cells 2023, 12(8), 1200; https://doi.org/10.3390/cells12081200 - 20 Apr 2023
Cited by 4 | Viewed by 2247
Abstract
Patients diagnosed with isocitrate dehydrogenase mutant (IDHmut) gliomas suffer frequently from seizures. Although the clinical course is less aggressive than that of its IDH wildtype counterpart, recent discoveries have shown that epileptic activity can promote tumor proliferation. However, it is not [...] Read more.
Patients diagnosed with isocitrate dehydrogenase mutant (IDHmut) gliomas suffer frequently from seizures. Although the clinical course is less aggressive than that of its IDH wildtype counterpart, recent discoveries have shown that epileptic activity can promote tumor proliferation. However, it is not known if antiepileptic drugs confer additional value by inhibiting tumor growth. In this study, the antineoplastic properties of 20 FDA-approved antiepileptic drugs (AEDs) were tested in six patient-derived IDHmut glioma stem-like cells (GSCs). Cell proliferation was assessed using the CellTiterGlo-3D assay. Two of the screened drugs (oxcarbazepine and perampanel) demonstrated an antiproliferative effect. A subsequent eight-point dose–response curve proved the dose-dependent growth inhibition for both drugs, but only oxcarbazepine reached an IC50 value below 100 µM in 5/6 GSCs (mean 44.7 µM; range 17.4–98.0 µM), approximating the possible cmax for oxcarbazepine in patient serums. Furthermore, the treated GSC spheroids were 82% smaller (mean volume 1.6 nL vs. 8.7 nL; p = 0.01 (live/deadTM fluorescence staining)), and the apoptotic events increased by more than 50% (caspase-3/7 activity; p = 0.006). Taken together, this drug screen of a large series of antiepileptic drugs identified oxcarbazepine as a potent proapoptotic drug in IDHmut GSCs, which combines antiepileptic and antineoplastic properties to treat this seizure-prone patient population. Full article
(This article belongs to the Special Issue Cancer Stem-Like Cells and Cancer Therapeutic Strategy)
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Review

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22 pages, 2208 KiB  
Review
Tumor Microenvironment Role in Pancreatic Cancer Stem Cells
by Aaron Galindo-Vega, Vilma Maldonado-Lagunas, Irma B. Mitre-Aguilar and Jorge Melendez-Zajgla
Cells 2023, 12(12), 1560; https://doi.org/10.3390/cells12121560 - 6 Jun 2023
Cited by 3 | Viewed by 2906
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a majority of patients presenting with unresectable or metastatic disease, resulting in a poor 5-year survival rate. This, in turn, is due to a highly complex tumor microenvironment and the presence of cancer [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a majority of patients presenting with unresectable or metastatic disease, resulting in a poor 5-year survival rate. This, in turn, is due to a highly complex tumor microenvironment and the presence of cancer stem cells, both of which induce therapy resistance and tumor relapse. Therefore, understanding and targeting the tumor microenvironment and cancer stem cells may be key strategies for designing effective PDAC therapies. In the present review, we summarized recent advances in the role of tumor microenvironment in pancreatic neoplastic progression. Full article
(This article belongs to the Special Issue Cancer Stem-Like Cells and Cancer Therapeutic Strategy)
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27 pages, 1264 KiB  
Review
Preclinical and Clinical Trials of New Treatment Strategies Targeting Cancer Stem Cells in Subtypes of Breast Cancer
by Natalia Landeros, Iván Castillo and Ramón Pérez-Castro
Cells 2023, 12(5), 720; https://doi.org/10.3390/cells12050720 - 24 Feb 2023
Cited by 11 | Viewed by 3494
Abstract
Breast cancer (BC) can be classified into various histological subtypes, each associated with different prognoses and treatment options, including surgery, radiation, chemotherapy, and endocrine therapy. Despite advances in this area, many patients still face treatment failure, the risk of metastasis, and disease recurrence, [...] Read more.
Breast cancer (BC) can be classified into various histological subtypes, each associated with different prognoses and treatment options, including surgery, radiation, chemotherapy, and endocrine therapy. Despite advances in this area, many patients still face treatment failure, the risk of metastasis, and disease recurrence, which can ultimately lead to death. Mammary tumors, like other solid tumors, contain a population of small cells known as cancer stem-like cells (CSCs) that have high tumorigenic potential and are involved in cancer initiation, progression, metastasis, tumor recurrence, and resistance to therapy. Therefore, designing therapies specifically targeting at CSCs could help to control the growth of this cell population, leading to increased survival rates for BC patients. In this review, we discuss the characteristics of CSCs, their surface biomarkers, and the active signaling pathways associated with the acquisition of stemness in BC. We also cover preclinical and clinical studies that focus on evaluating new therapy systems targeted at CSCs in BC through various combinations of treatments, targeted delivery systems, and potential new drugs that inhibit the properties that allow these cells to survive and proliferate. Full article
(This article belongs to the Special Issue Cancer Stem-Like Cells and Cancer Therapeutic Strategy)
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