Immunotherapy: a potential approach to targeting cancer stem cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Wenjun Wang ◽  
Ling Bai ◽  
Dongsheng Xu ◽  
Wei Li ◽  
Jiuwei Cui
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Tumor Recurrence ◽  
Immune Cell ◽  
Key Factors ◽  
Cell Therapies ◽  
Factors Affecting ◽  
Therapeutic Milieu ◽  
Traditional Therapies

: Tumor recurrence and drug resistance are two of the key factors affecting the prognosis of cancer patients. Cancer stem cells (CSCs) are a group of cells with infinite proliferation potential which are not sensitive to traditional therapies including radio- and chemotherapy. These CSCs are considered to be central to tumor recurrence and the development of drug resistance. In addition, CSCs are important targets in cancer immunotherapy because of their expression of novel tumor-associated antigens, which result from mutations in cancer cells over the course of treatment. Emerging immunotherapies, including cancer vaccines, checkpoint blockade therapies, and transferred immune cell therapies, have all been shown to be more effective when they selectively target CSCs. Such therapies may also provide novel additions to the current therapeutic milieu and may offer new therapeutic combinations for treatment. This review summarizes the relationships between various immunotherapies and CSCs and provides novel insights into potential therapeutic applications for these approaches in the future.

Cancer stemness as a target for immunotherapy is shaped by pro-inflammatory stress.

2020 ◽  
Vol 15 ◽  
Author(s):  
Nese Unver
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Immune Cells ◽  
Tumor Recurrence ◽  
Inflammatory Factors ◽  
Cancer Stemness ◽  
Self Renewal ◽  
Inflammatory Stress ◽  
Factors Affecting

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.

scholarly journals Signaling Pathways Associated with Cancer Stem Cells Play a Significant Role in Immunotherapy Resistance

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Yajuan Zhu ◽  
Yuwen Zhou ◽  
Yao Xie ◽  
Pan Song ◽  
Xuelei Ma
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Tumor Recurrence ◽  
Underlying Mechanism ◽  
Self Renewal ◽  
Persistent Problem ◽  
Immune Resistance

Cancer stem cells (CSCs) are a subpopulation of tumor cells with properties of self-renewal, pluripotency, plasticity, and differentiation, and are associated with various aberrantly stimulated signaling pathways. They are responsible for tumor recurrence, distant metastasis, and drug resistance, thus inducing poor prognosis. Immunotherapy has achieved encouraging results. However, the resistance associated with its clinical application is a persistent problem in clinical and scientific researches. Increasing evidence shows that signaling pathways associated with CSCs mediate immunotherapy resistance. This review highlights the link between them, and focuses on the underlying mechanism so as to provide potential strategies and approaches for the development of new targets against the immune resistance challenge.

scholarly journals Repositioning Trimebutine Maleate as a Cancer Treatment Targeting Ovarian Cancer Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 918
Author(s):  
Heejin Lee ◽  
Oh-Bin Kwon ◽  
Jae-Eon Lee ◽  
Yong-Hyun Jeon ◽  
Dong-Seok Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Ovarian Cancer Cells ◽  
Therapeutic Drug ◽  
G1 Arrest ◽  
Dead Cell ◽  
Trimebutine Maleate ◽  
Simultaneous Inhibition

The overall five-year survival rate for late-stage patients of ovarian cancer is below 29% due to disease recurrence and drug resistance. Cancer stem cells (CSCs) are known as a major contributor to drug resistance and recurrence. Accordingly, therapies targeting ovarian CSCs are needed to overcome the limitations of present treatments. This study evaluated the effect of trimebutine maleate (TM) targeting ovarian CSCs, using A2780-SP cells acquired by a sphere culture of A2780 epithelial ovarian cancer cells. TM is indicated as a gastrointestinal motility modulator and is known to as a peripheral opioid receptor agonist and a blocker for various channels. The GI50 of TM was approximately 0.4 µM in A2780-SP cells but over 100 µM in A2780 cells, demonstrating CSCs specific growth inhibition. TM induced G0/G1 arrest and increased the AV+/PI+ dead cell population in the A2780-SP samples. Furthermore, TM treatment significantly reduced tumor growth in A2780-SP xenograft mice. Voltage gated calcium channels (VGCC) and calcium-activated potassium channels (BKCa) were overexpressed on ovarian CSCs and targeted by TM; inhibition of both channels reduced A2780-SP cells viability. TM reduced stemness-related protein expression; this tendency was reproduced by the simultaneous inhibition of VGCC and BKCa compared to single channel inhibition. In addition, TM suppressed the Wnt/β-catenin, Notch, and Hedgehog pathways which contribute to many CSCs characteristics. Specifically, further suppression of the Wnt/β-catenin pathway by simultaneous inhibition of BKCa and VGCC is necessary for the effective and selective action of TM. Taken together, TM is a potential therapeutic drug for preventing ovarian cancer recurrence and drug resistance.

The impact of fusion genes on cancer stem cells and drug resistance

2021 ◽  
Author(s):  
Saurav Panicker ◽  
Sivaramakrishnan Venkatabalasubramanian ◽  
Surajit Pathak ◽  
Satish Ramalingam
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Fusion Genes ◽  
The Impact

scholarly journals Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kristen Abernathy ◽  
Jeremy Burke
Keyword(s):  
Stem Cells ◽  
Glioblastoma Multiforme ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Differential Equations ◽  
Ordinary Differential Equations ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Common Event

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

Natural products targeting cancer stem cells: a revisit

2021 ◽  
Vol 28 ◽  
Author(s):  
Jiahua Cui ◽  
Jiajun Qian ◽  
Larry Ming-Cheung Chow ◽  
Jinping Jia
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Therapeutic Potential ◽  
Tumor Development ◽  
Biologically Active ◽  
Cellular Targets ◽  
Drug Candidates ◽  
Enhanced Expression

Background: The proposed central role of cancer stem cells (CSCs) in tumor development has been extended to explain the diverse oncologic phenomena such as multidrug resistance, metastasis and tumor recurrence in clinics. Due to the enhanced expression of ATP-binding cassette transporters and anti-apoptotic factors, stagnation on G0 phase and the strong ability of self-renewal, the CSCs were highly resistant to clinical anticancer drugs. Therefore, the discovery of new drug candidates that could effectively eradicate cancer stem cells afforded promising outcomes in cancer therapy. Introduction: Natural products and their synthetic analogues are a rich source of biologically active compounds and several of them have already been recognized as potent CSCs killers. We aim to provide a collection of recently identified natural products that suppressed the survival of the small invasive CSC populations and combated the drug resistance of these cells in chemotherapy. Results and Conclusion: These anti-CSCs natural products included flavonoids, stilbenes, quinones, terpenoids, polyketide antibiotics, steroids and alkaloids. In the present review, we highlighted the therapeutic potential of natural products and their derivatives against the proliferation and drug resistance of CSCs, their working mechanisms and related structure-activity relationships. Meanwhile, in this survey, several natural products with diverse cellular targets such as the naphthoquinone shikonin and the stilbene resveratrol were characterized as promising lead compounds for future development.

scholarly journals Long noncoding RNA LINC00261 upregulates ITIH5 to impair tumorigenic ability of pancreatic cancer stem cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Lijuan Zou ◽  
Hengpeng He ◽  
Zhiguo Li ◽  
Ou Chen ◽  
Xiukun Jia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Noncoding Rna ◽  
Cell Subset ◽  
Luciferase Reporter ◽  
Stem Cell Markers ◽  
Self Renewal

AbstractLong noncoding RNAs (lncRNAs) are implicated tumor development in a range of different cancers, including pancreatic cancer (PC). Cancer stem cells (CSCs), a drug-resistant cancer cell subset, drive tumor progression in PC. In this work, we aimed to investigate the mechanism by which lncRNA LINC00261 affects the biological functions of CSCs during the progression of PC. Microarray analysis of differentially expressed genes and lncRNAs suggested that LINC00261 is downregulated in PC. Both LINC00261 and ITIH5 were confirmed to be downregulated in PC cells and PC stem cells. Gain-of-function and loss-of-function investigations were performed to analyze their effects on cell proliferation, drug resistance, cell cycle distribution, self-renewal, invasion, and ultimately overall tumorigenicity. These experiments revealed that the expression of stem cell markers was reduced, and cell proliferation, self-renewal ability, cell invasion, drug resistance, and tumorigenicity were all suppressed by upregulation of LINC00261 or ITIH5. The results of dual-luciferase reporter gene, ChIP, and RIP assays indicated that LINC00261 binds directly to GATA6, increasing its activity at the ITIH5 promoter. The presence of LINC00261 and GATA6 inhibited the self-renewal and tumorigenesis of PC stem cells, while silence of ITIH5 rescued those functions. Collectively, this study identifies the tumor suppressive activity of LINC00261 in PC, showing that this lncRNA limits the functions of PC stem through an ITIH5/GATA6 regulatory pathway.

Colon cancer: Cancer stem cells markers, drug resistance and treatment

2014 ◽  
Vol 68 (8) ◽  
pp. 911-916 ◽  
Author(s):  
Zuzana Kozovska ◽  
Veronika Gabrisova ◽  
Lucia Kucerova
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Stem Cells
Sign in / Sign up

Export Citation Format

Share Document