Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies

2021 ◽  
Vol 16 ◽  
Author(s):  
Dunne Fong ◽  
Chase T. Christensen ◽  
Marion M. Chan
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Care ◽  
Cancer Metastasis ◽  
Psychotic Disorders ◽  
Inflammatory Diseases ◽  
Fatal Outcome ◽  
Cell Types ◽  
Repurposed Drugs

Background: Cancer is a multistep process involving genetic and epigenetic changes in the somatic genome. Genetic mutations as well as environmental factors lead to the initiation, promotion, and progression of cancer. Metastasis allows cancer cells to spread via circulatory and lymphatic systems; secondary tumorigenesis typically leads to a fatal outcome. Recent experimental evidence suggests Cancer Stem Cells (CSCs) play a pivotal role in tumor progression. A tumor is heterogeneous and composed of different cell types. CSCs are a subpopulation of tumor cells possessing abilities to self-renew and differentiate. Objective: To present repurposed drugs, and potential candidates, that can serve as anticancer medications intended to target resistant cancer cells, i.e. CSCs. Methods: Research publications, FDA filings, and patents have been reviewed for repurposed drugs or drug combinations that can act to improve cancer care. Results: Drugs that act against CSCs include ones approved for treatment of diabetes (metformin & thiazolidinediones), parasitic diseases (chloroquine, niclosamide, mebendazole & pyrvinium), psychotic disorders (thioridazine, clomipramine & phenothiazines), alcoholism (disulfiram), lipid disorder (statins), inflammatory diseases (tranilast, auranofin, acetaminophen & celecoxib), antibiotics (azithromycin), and other disorders. Current research findings advocate the existence of beneficial effects by combining these repurposed drugs, and also through their complementary use with conventional cancer therapies. Conclusion: Repurposing FDA-approved medications towards cancer care, by targeting the resistant CSCs, will allow for a quicker, cheaper development and approval process. A larger drug library available to physicians will allow for increased efficacy during both first-line and recurrent cancer treatments.

scholarly journals Ovarian Cancer Stemness: Biological and Clinical Implications for Metastasis and Chemotherapy Resistance

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 907 ◽  
Author(s):  
Takeshi Motohara ◽  
Hidetaka Katabuchi
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Chemotherapy Resistance ◽  
Clinical Implications ◽  
Ovarian Cancer Stem Cells

Epithelial ovarian cancer is a highly lethal gynecological malignancy that is characterized by the early development of disseminated metastasis. Though ovarian cancer has been generally considered to preferentially metastasize via direct transcoelomic dissemination instead of the hematogenous route, emerging evidence has indicated that the hematogenous spread of cancer cells plays a larger role in ovarian cancer metastasis than previously thought. Considering the distinctive biology of ovarian cancer, an in-depth understanding of the biological and molecular mechanisms that drive metastasis is critical for developing effective therapeutic strategies against this fatal disease. The recent “cancer stem cell theory” postulates that cancer stem cells are principally responsible for tumor initiation, metastasis, and chemotherapy resistance. Even though the hallmarks of ovarian cancer stem cells have not yet been completely elucidated, metastasized ovarian cancer cells, which have a high degree of chemoresistance, seem to manifest cancer stem cell properties and play a key role during relapse at metastatic sites. Herein, we review our current understanding of the cell-biological mechanisms that regulate ovarian cancer metastasis and chemotherapy resistance, with a pivotal focus on ovarian cancer stem cells, and discuss the potential clinical implications of evolving cancer stem cell research and resultant novel therapeutic approaches.

scholarly journals Wnt signaling in cancer stem cells and colon cancer metastasis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 699 ◽  
Author(s):  
Sayon Basu ◽  
Gal Haase ◽  
Avri Ben-Ze'ev
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Cell Types ◽  
Upward Movement ◽  
Signature Genes ◽  
Normal Intestine ◽  
Small Subpopulation

Overactivation of Wnt signaling is a hallmark of colorectal cancer (CRC). The Wnt pathway is a key regulator of both the early and the later, more invasive, stages of CRC development. In the normal intestine and colon, Wnt signaling controls the homeostasis of intestinal stem cells (ISCs) that fuel, via proliferation, upward movement of progeny cells from the crypt bottom toward the villus and differentiation into all cell types that constitute the intestine. Studies in recent years suggested that cancer stem cells (CSCs), similar to ISCs of the crypts, consist of a small subpopulation of the tumor and are responsible for the initiation and progression of the disease. Although various ISC signature genes were also identified as CRC markers and some of these genes were even demonstrated to have a direct functional role in CRC development, the origin of CSCs and their contribution to cancer progression is still debated. Here, we describe studies supporting a relationship between Wnt-regulated CSCs and the progression of CRC.

scholarly journals Dynamism, Sensitivity, and Consequences of Mesenchymal and Stem-Like Phenotype of Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Petra Gener ◽  
Joaquin Seras-Franzoso ◽  
Patricia González Callejo ◽  
Fernanda Andrade ◽  
Diana Rafael ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cell Types ◽  
Mesenchymal Phenotype ◽  
Metastatic Growth ◽  
Anticancer Treatment

There are remarkable similarities in the description of cancer stem cells (CSCs) and cancer cells with mesenchymal phenotype. Both cell types are highly tumorigenic, resistant against common anticancer treatment, and thought to cause metastatic growth. Moreover, cancer cells are able to switch between CSC and non-CSC phenotypes and vice versa, to ensure the necessary balance within the tumor. Likewise, cancer cells can switch between epithelial and mesenchymal phenotypes via well-described transition (EMT/MET) that is thought to be crucial for tumor propagation. In this review, we discuss whether, and to which extend, the CSCs and mesenchymal cancer cells are overlapping phenomena in terms of mechanisms, origin, and implication for cancer treatment. As well, we describe the dynamism of both phenotypes and involvement of the tumor microenvironment in CSC reversion and in EMT.

Targeting Cancer Stem Cells and Non-Stem Cancer Cells: The Potential of Lipid- Based Nanoparticles

2018 ◽  
Vol 23 (43) ◽  
pp. 6563-6572
Author(s):  
Ana Filipa Cruz ◽  
Nuno Andre Fonseca ◽  
Vera Moura ◽  
Sergio Simoes ◽  
Joao Nuno Moreira
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells

Biological Aspects and Clinical Applications of Mesenchymal Stem Cells: Key Features You Need to be Aware of.

2020 ◽  
Vol 21 ◽  
Author(s):  
Mohammad Saeedi ◽  
Muhammad Sadeqi Nezhad ◽  
Fatemeh Mehranfar ◽  
Mahdieh Golpour ◽  
Mohammad Ali Esakandari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Immune Modulation ◽  
Adult Stem Cells ◽  
Inflammatory Diseases ◽  
High Capacity ◽  
Genetically Engineered ◽  
Cartilage Cells ◽  
Biological Aspects

: Mesenchymal stem cells (MSCs), a form of adult stem cells, are known to have a self-renewing property and the potential to specialize into a multitude of cells and tissues such as adipocytes, cartilage cells, and fibroblasts. MSCs can migrate and home to the desired target zone where inflammation is present. The unique characteristics of MSCs in repairing, differentiation, regeneration, and its high capacity of immune modulation has attracted tremendous attention for exerting them in clinical purposes, as they contribute to tissue regeneration process and anti-tumor activity. The MSCs-based treatment has demonstrated remarkable applicability towards various diseases such as heart and bone malignancies, and cancer cells. Importantly, genetically engineered MSCs, as a state-of-the-art therapeutic approach, could address some clinical hurdles by systemic secretion of cytokines and other agents with a short half-life and high toxicity. Therefore, understanding the biological aspects and the characteristics of MSCs is an imperative issue of concern. Herein, we provide an overview of the therapeutic application and the biological features of MSCs against different inflammatory diseases and cancer cells. We further shed light on MSCs physiological interaction, such as migration, homing, and tissue repairing mechanisms with different healthy and inflamed tissues.

Comparison of the Growth Curves of Cancer Cells and Cancer Stem Cells

2014 ◽  
Vol 9 (2) ◽  
pp. 112-116 ◽  
Author(s):  
Maria Toloudi ◽  
Eleni Ioannou ◽  
Marina Chatziioannou ◽  
Panagiotis Apostolou ◽  
Christos Kiritsis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Growth Curves

Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Shahram Taeb ◽  
Hamed Haghi-Aminjan ◽  
Shima Afrashi ◽  
Kave Moloudi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Fas Ligand ◽  
Inhibitory Effect ◽  
Mitochondrial Pathway ◽  
Multi Drug Resistance ◽  
Chemotherapy Drugs ◽  
Normal Tissues ◽  
Anti Cancer

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

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