Seeding drug discovery: integrating telomerase cancer biology and cellular senescence to uncover new therapeutic opportunities in targeting cancer stem cells

2007 ◽  
Vol 12 (15-16) ◽  
pp. 611-621 ◽  
Author(s):  
W KEITH ◽  
C THOMSON ◽  
J HOWCROFT ◽  
N MAITLAND ◽  
J SHAY
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Cancer Stem Cells ◽  
Cellular Senescence ◽  
Cancer Biology

scholarly journals Erratum: Drug Discovery Approaches to Target Wnt Signaling in Cancer Stem Cells

Oncotarget ◽  
2018 ◽  
Vol 9 (78) ◽  
pp. 34856-34856 ◽  
Author(s):  
Joshua C. Curtin ◽  
Matthew V. Lorenzi
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Cancer Stem Cells ◽  
Wnt Signaling

scholarly journals Novel drug discovery system for cancer stem cells in human squamous cell carcinoma of the esophagus

2013 ◽  
Vol 31 (3) ◽  
pp. 1133-1138 ◽  
Author(s):  
YOSHIHIRO KANO ◽  
MASAMITSU KONNO ◽  
KOICHI KAWAMOTO ◽  
KEISUKE TAMARI ◽  
KAZUHIKO HAYASHI ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Drug Discovery ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Carcinoma Of The Esophagus ◽  
Human Squamous Cell Carcinoma ◽  
Discovery System ◽  
Novel Drug

scholarly journals Gastric Cancer Stem Cells

2008 ◽  
Vol 26 (17) ◽  
pp. 2876-2882 ◽  
Author(s):  
Shigeo Takaishi ◽  
Tomoyuki Okumura ◽  
Timothy C. Wang
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cell Biology ◽  
Cancer Biology ◽  
Human Cancer ◽  
Immunodeficient Mice

Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony formation in serum-free media in vitro, as well as tumorigenic ability in immunodeficient mice in vivo. We will also discuss the possible origins of the gastric cancer stem cell from an organ-specific stem cell versus a recently recognized new candidate bone marrow–derived cell (BMDC). We have previously shown that BMDC contributed to malignant epithelial cells in the mouse model of Helicobacter-associated gastric cancer. On the basis of these findings from animal model, we propose that a similar phenomenon may also occur in human cancer biology, particularly in the cancer origin of other inflammation-associated cancers. The expanding research field of cancer stem-cell biology may offer a novel clinical apparatus to the diagnosis and treatment of cancer.

scholarly journals B4GALT1 Is a New Candidate to Maintain the Stemness of Lung Cancer Stem Cells

2019 ◽  
Vol 8 (11) ◽  
pp. 1928 ◽  
Author(s):  
Claudia De Vitis ◽  
Giacomo Corleone ◽  
Valentina Salvati ◽  
Francesca Ascenzi ◽  
Matteo Pallocca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Biology ◽  
High Throughput Sequencing ◽  
Primary Cultures ◽  
Disease Recurrence ◽  
Chromatin Accessibility ◽  
Rna Seq ◽  
3D Cultures ◽  
Lung Cancer Stem Cells

Background: According to the cancer stem cells (CSCs) hypothesis, a population of cancer cells with stem cell properties is responsible for tumor propagation, drug resistance, and disease recurrence. Study of the mechanisms responsible for lung CSCs propagation is expected to provide better understanding of cancer biology and new opportunities for therapy. Methods: The Lung Adenocarcinoma (LUAD) NCI-H460 cell line was grown either as 2D or as 3D cultures. Transcriptomic and genome-wide chromatin accessibility studies of 2D vs. 3D cultures were carried out using RNA-sequencing and Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), respectively. Reverse transcription polymerase chain reaction (RT-PCR) was also carried out on RNA extracted from primary cultures derived from malignant pleural effusions to validate RNA-seq results. Results: RNA-seq and ATAC-seq data disentangled transcriptional and genome accessibility variability of 3D vs. 2D cultures in NCI-H460 cells. The examination of genomic landscape of genes upregulated in 3D vs. 2D cultures led to the identification of 2D cultures led to the identification of Beta-1,4-galactosyltranferase 1 (B4GALT1) as the top candidate. B4GALT1 as the top candidate. B4GALT1 was validated as a stemness factor, since its silencing caused strong inhibition of 3D spheroid formation. Conclusion: Combined transcriptomic and chromatin accessibility study of 3D vs. 2D LUAD cultures led to the identification of B4GALT1 as a new factor involved in the propagation and maintenance of LUAD CSCs.

scholarly journals Communication Between Epithelial–Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaobo Zheng ◽  
Fuzhen Dai ◽  
Lei Feng ◽  
Hong Zou ◽  
Li Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Mesenchymal Transition ◽  
Binary Model ◽  
Epithelial Phenotype

The epithelial–mesenchymal transition (EMT) is closely associated with the acquisition of aggressive traits by carcinoma cells and is considered responsible for metastasis, relapse, and chemoresistance. Molecular links between the EMT and cancer stem cells (CSCs) have indicated that EMT processes play important roles in the expression of CSC-like properties. It is generally thought that EMT-related transcription factors (EMT-TFs) need to be downregulated to confer an epithelial phenotype to mesenchymal cells and increase cell proliferation, thereby promoting metastasis formation. However, the genetic and epigenetic mechanisms that regulate EMT and CSC activation are contradictory. Emerging evidence suggests that EMT need not be a binary model and instead a hybrid epithelial/mesenchymal state. This dynamic process correlates with epithelial–mesenchymal plasticity, which indicates a contradictory role of EMT during cancer progression. Recent studies have linked the epithelial–mesenchymal plasticity and stem cell-like traits, providing new insights into the conflicting relationship between EMT and CSCs. In this review, we examine the current knowledge about the interplay between epithelial–mesenchymal plasticity and CSCs in cancer biology and evaluate the controversies and future perspectives. Understanding the biology of epithelial–mesenchymal plasticity and CSCs and their implications in therapeutic treatment may provide new opportunities for targeted intervention.

Conditional Generative Adversarial Networks to Model iPSC-Derived Cancer Stem Cells

2020 ◽  
Vol 24 (1) ◽  
pp. 134-141 ◽  
Author(s):  
Saori Aida ◽  
Hiroyuki Kameda ◽  
Sakae Nishisako ◽  
Tomonari Kasai ◽  
Atsushi Sato ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Stem Cells ◽  
Drug Discovery ◽  
Cancer Stem Cells ◽  
Low Cost ◽  
Generative Adversarial Networks ◽  
Cell Detection ◽  
Smart System ◽  
Adversarial Networks ◽  
Normal Image

The realization of effective and low-cost drug discovery is imperative to enable people to easily purchase and use medicines when necessary. This paper reports a smart system for detecting iPSC-derived cancer stem cells by using conditional generative adversarial networks. This system with artificial intelligence (AI) accepts a normal image from a microscope and transforms it into a corresponding fluorescent-marked fake image. The AI system learns 10,221 sets of paired pictures as input. Consequently, the system’s performance shows that the correlation between true fluorescent-marked images and fake fluorescent-marked images is at most 0.80. This suggests the fundamental validity and feasibility of our proposed system. Moreover, this research opens a new way for AI-based drug discovery in the process of iPSC-derived cancer stem cell detection.

Existing drugs and their application in drug discovery targeting cancer stem cells

2015 ◽  
Vol 38 (9) ◽  
pp. 1617-1626 ◽  
Author(s):  
Junfang Lv ◽  
Joong Sup Shim
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Cancer Stem Cells

Cancer stem cells as a target population for drug discovery

2014 ◽  
Vol 6 (14) ◽  
pp. 1567-1585 ◽  
Author(s):  
Claire Bouvard ◽  
Colleen Barefield ◽  
Shoutian Zhu
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Cancer Stem Cells ◽  
Target Population

scholarly journals FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sébastien Relier ◽  
Julie Ripoll ◽  
Hélène Guillorit ◽  
Amandine Amalric ◽  
Cyrinne Achour ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Biological Function ◽  
Cancer Management ◽  
Demethylase Activity

AbstractCancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise to metastases. Despite accruing evidence establishing a link between deregulation of epitranscriptome-related players and tumorigenic process, the role of messenger RNA (mRNA) modifications in the regulation of CSC properties remains poorly understood. Here, we show that the cytoplasmic pool of fat mass and obesity-associated protein (FTO) impedes CSC abilities in colorectal cancer through its N6,2’-O-dimethyladenosine (m6Am) demethylase activity. While m6Am is strategically located next to the m7G-mRNA cap, its biological function is not well understood and has not been addressed in cancer. Low FTO expression in patient-derived cell lines elevates m6Am level in mRNA which results in enhanced in vivo tumorigenicity and chemoresistance. Inhibition of the nuclear m6Am methyltransferase, PCIF1/CAPAM, fully reverses this phenotype, stressing the role of m6Am modification in stem-like properties acquisition. FTO-mediated regulation of m6Am marking constitutes a reversible pathway controlling CSC abilities. Altogether, our findings bring to light the first biological function of the m6Am modification and its potential adverse consequences for colorectal cancer management.

scholarly journals Heterogeneity of Cancer Stem Cells in Tumorigenesis, Metastasis, and Resistance to Antineoplastic Treatment of Head and Neck Tumours

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3068
Author(s):  
Nicola Cirillo ◽  
Carmen Wu ◽  
Stephen S. Prime
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Head And Neck ◽  
Cancer Biology ◽  
Therapeutic Strategy ◽  
Side Population ◽  
Small Subset ◽  
Head And Neck Tumours ◽  
Antineoplastic Treatment

The discovery of a small subset of cancer cells with self-renewal properties that can give rise to phenotypically diverse tumour populations has shifted our understanding of cancer biology. Targeting cancer stem cells (CSCs) is becoming a promising therapeutic strategy in various malignancies, including head and neck squamous cell carcinoma (HNSCC). Diverse sub-populations of head and neck cancer stem cells (HNCSCs) have been identified previously using CSC specific markers, the most common being CD44, Aldehyde Dehydrogenase 1 (ALDH1), and CD133, or by side population assays. Interestingly, distinct HNCSC subsets play different roles in the generation and progression of tumours. This article aims to review the evidence for a role of specific CSCs in HNSCC tumorigenesis, invasion, and metastasis, together with resistance to treatment.

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