scholarly journals The role of cancer stem cells in tumor heterogeneity and resistance to therapy

2017 ◽  
Vol 95 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Christina Valbirk Konrad ◽  
Reshma Murali ◽  
Binitha Anu Varghese ◽  
Radhika Nair
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Therapy Resistance ◽  
Cellular Mechanisms ◽  
Resistance To Therapy ◽  
Repair Mechanisms ◽  
Cancer Types ◽  
Survival Signaling

Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients. The cellular mechanisms of therapy resistance in CSCs are ascribed to several factors including a state of quiescence, an enhanced DNA damage response and active repair mechanisms, up-regulated expression of drug efflux transporters, as well as the activation of pro-survival signaling pathways and inactivation of apoptotic signaling. Understanding the mechanisms underlying the acquisition of resistance to therapy may hold the key to targeting the CSC population.

scholarly journals Mechanisms of Anticancer Therapy Resistance: The Role of Cancer Stem Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9006
Author(s):  
Julhash U. Kazi
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Patients ◽  
Anticancer Therapy ◽  
Therapy Resistance ◽  
Resistance To Therapy ◽  
Therapy Development

Despite incredible progress in anticancer therapy development, resistance to therapy is the major factor limiting the cure of cancer patients [...]

scholarly journals Different Shades of L1CAM in the Pathophysiology of Cancer Stem Cells

2020 ◽  
Vol 9 (5) ◽  
pp. 1502 ◽  
Author(s):  
Marco Giordano ◽  
Ugo Cavallaro
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Biological Properties ◽  
Cytotoxic Agents ◽  
Tumor Initiating Cells ◽  
Mesenchymal Transition ◽  
Tumor Types

L1 cell adhesion molecule (L1CAM) is aberrantly expressed in several tumor types where it is causally linked to malignancy and therapy resistance, acting also as a poor prognosis factor. Accordingly, several approaches have been developed to interfere with L1CAM function or to deliver cytotoxic agents to L1CAM-expressing tumors. Metastatic dissemination, tumor relapse and drug resistance can be fueled by a subpopulation of neoplastic cells endowed with peculiar biological properties that include self-renewal, efficient DNA repair, drug efflux machineries, quiescence, and immune evasion. These cells, known as cancer stem cells (CSC) or tumor-initiating cells, represent, therefore, an ideal target for tumor eradication. However, the molecular and functional traits of CSC have been unveiled only to a limited extent. In this context, it appears that L1CAM is expressed in the CSC compartment of certain tumors, where it plays a causal role in stemness itself and/or in biological processes intimately associated with CSC (e.g., epithelial-mesenchymal transition (EMT) and chemoresistance). This review summarizes the role of L1CAM in cancer focusing on its functional contribution to CSC pathophysiology. We also discuss the clinical usefulness of therapeutic strategies aimed at targeting L1CAM in the context of anti-CSC treatments.

scholarly journals Role of Cancer Stem Cells in Spine Tumors

Neurosurgery ◽  
2012 ◽  
Vol 71 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Wesley Hsu ◽  
Ahmed Mohyeldin ◽  
Sagar R. Shah ◽  
Ziya L. Gokaslan ◽  
Alfredo Quinones-Hinojosa
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Surgical Intervention ◽  
Spinal Column ◽  
Primary Tumors ◽  
Tumorigenic Potential ◽  
Active Investigation

Abstract The management of spinal column tumors continues to be a challenge for clinicians. The mechanisms of tumor recurrence after surgical intervention as well as resistance to radiation and chemotherapy continue to be elucidated. Furthermore, the pathophysiology of metastatic spread remains an area of active investigation. There is a growing body of evidence pointing to the existence of a subset of tumor cells with high tumorigenic potential in many spine cancers that exhibit characteristics similar to those of stem cells. The ability to self-renew and differentiate into multiple lineages is the hallmark of stem cells, and tumor cells that exhibit these characteristics have been described as cancer stem cells (CSCs). The mechanisms that allow nonmalignant stem cells to promote normal developmental programming by way of enhanced proliferation, promotion of angiogenesis, and increased motility may be used by CSCs to fuel carcinogenesis. The purpose of this review is to discuss what is known about the role of CSCs in tumors of the osseous spine. First, this article reviews the fundamental concepts critical to understanding the role of CSCs with respect to chemoresistance, radioresistance, and metastatic disease. This discussion is followed by a review of what is known about the role of CSCs in the most common primary tumors of the osseous spine.

Role of Aberrant Lipid Metabolism of Cancer Stem Cells in Cancer Progression

2021 ◽  
Vol 21 ◽  
Author(s):  
Juan Zhou ◽  
Jing Zhao ◽  
Chunxia Su
Keyword(s):  
Stem Cells ◽  
Lipid Metabolism ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Energy Homeostasis ◽  
Small Population ◽  
Research Field ◽  
Metabolic Reprogramming ◽  
Cancer Types

: Cancer stem cells (CSCs) represent a small population of cancer cells that are able to self-renew and initiate tumors, which undergo epigenetic, epithelial-mesenchymal, immunological, and metabolic reprogramming to adapt to the tumor microenvironment as well as survive host defense or therapeutic insults. The metabolic reprogramming that accompanies cancer onset is known to be critical for the disease pathogenesis. A coordinated dysregulation of lipid metabolism is observed in nearly all cancer types. In addition to fulfilling basic requirements of structural lipids for membrane synthesis, lipids function importantly as signaling molecules and contribute to energy homeostasis. In this review, we summarize the current progress in the attractive research field of aberrant lipid metabolism regarding CSCs in cancer progression, which provides insights into therapeutic agents targeting CSCs based upon their modulation of lipid metabolism.

Lung Cancer Stem Cells: An Epigenetic Perspective

2017 ◽  
Vol 18 (1) ◽  
pp. 16-31 ◽  
Author(s):  
Samriddhi Shukla ◽  
Sajid Khan ◽  
Sonam Sinha ◽  
Syed Musthapa Meeran
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epigenetic Modifications ◽  
Normal Lung ◽  
Stem Cell Markers ◽  
Lung Epithelium ◽  
Lung Cancer Stem Cells ◽  
Cancer Types

Lung cancer remains the major cause of human mortality among all the cancer types despite the colossal amount of efforts to prevent the cancer onset and to provide the appropriate cure. Recent reports have identified that important contributors of lung cancer-related mortality are the drug resistance and aggressive tumor relapse, the characteristics contributed by the presence of lung cancer stem cells (CSCs). The identification of lung CSCs is inherently complex due to the quiescent nature of lung epithelium, which makes the distinction between the normal lung epithelium and lung CSCs difficult. Recently, multiple researches have helped in the identification of lung CSCs based on the presence or absence of certain specific types of stem cell markers. Maintenance of lung CSCs is chiefly mediated through the epigenetic modifications of their genome. In this review, we will discuss about the origin of lung CSCs and the role of epigenetic modifications in their maintenance. We will also discuss in brief the major lung CSC markers and the therapeutic approaches to selectively target this population of cells.

Role of circulating tumor cells and cancer stem cells in hepatocellular carcinoma

2014 ◽  
Vol 8 (3) ◽  
pp. 321-329 ◽  
Author(s):  
Ivonne Nel ◽  
Paul David ◽  
Guido G. H. Gerken ◽  
Joerg F. Schlaak ◽  
Andreas-Claudius Hoffmann
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells

scholarly journals A2 KRT15+ TUMOR CELLS AS PUTATIVE CANCER STEM CELLS IN ESOPHAGEAL CANCER.

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 2-3
Author(s):  
J Douchin ◽  
V Giroux
Keyword(s):  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Treatment Resistance ◽  
Esophageal Tumor ◽  
Basal Cells ◽  
Cell Of Origin ◽  
Self Renewal

Abstract Background Esophageal cancer is a particularly deadly cancer with a 5-year survival rate of only 14% in Canada. Treatment resistance ascribed for at least 30% of the death. The acquisition of resistance to radio- and chemotherapy is mostly attributed to the presence of cancer stem cells (CSCs) and their persistence following classical treatments. CSCs are a subpopulation of tumor cells with high self-renewal and multipotent capacity which amongst others contribute to tumor heterogeneity. Our previous work identified Krt15+ esophageal cells as a rare and long-lived subpopulation of basal cells with higher self-renewal and multipotent capacities than other basal cells. Furthermore, preliminary observations suggest that Krt15+ cells could act as the cell-of-origin for ESCC, the most prevalent type of esophageal cancer worldwide. Though, we still ignore the role of Krt15+ cells in later stages of esophageal cancer such as treatment resistance and if therefore, they could act as CSC. Aims Determine if Krt15+ cells act as CSCs in ESCC patients and if they could contribute to treatment resistance. Methods To do so, we used Krt15-CrePR1;R26mT/mG mice treated with the carcinogen 4 Nitroquinoline-1-oxide (4NQO) in their drinking water for 16 weeks to induce ESCC. Twelve weeks following the beginning of 4NQO treatment, we induced Cre recombination with RU486, a PR1 agonist, leading to GFP expression specifically in Krt15+ cells. Following 4NQO treatment, mice were put back on normal water for 8 to 12 weeks allowing tumors to grow. At euthanasia, esophageal tumor cells were FACS sorted to isolate Krt15+ (GFP+) and Krt15- (GFP-) cells, which were then grown as tumoroids. Results We first validated that 4NQO successfully induced the formation of esophageal lesions in our model, which comprises Krt15+ and Krt15- tumor cells. Tumoroids were then successfully derived from these FACS-sorted cell populations. We demonstrated the increase of CSC-like cells within Krt15+ tumoroids compared to Krt15- tumoroids by measuring the presence of CD44highCD24high cells, two well-known CSC markers, by flow cytometry. Interestingly, Krt15+ and Krt15- tumoroids are histologically distinct. As observed for normal cells, Krt15+ tumoroids appeared as more multipotent and heterogenous than Krt15- tumoroids. Furthermore, Krt15+ tumoroids display higher hyperplasia than Krt15- tumoroids suggesting that Krt15+ tumor cells are functionally distinct from Krt15- tumor cells. Conclusions Krt15+ tumoroids display higher CSC content and hyperplastic capacity suggesting their potential role in esophageal cancer. With this project, we aim to highlight the role of Krt15+ cells in treatment resistance and put forward new targets to overcome this deadly issue in ESCC patients. Funding Agencies CAGCanada research chair TIER 2

scholarly journals Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review

2020 ◽  
Author(s):  
Dimakatso Alice Senthebane ◽  
Chelene Ganz ◽  
Nicholas Ekow Thomford ◽  
Kevin Dzobo
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Treatment Strategies ◽  
Cancer Recurrence ◽  
Therapy Resistance ◽  
Repair Mechanisms ◽  
Microenvironmental Factors ◽  
Novel Treatment Strategies

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance, culminating in relapse and metastatic disease continue to be associated with fatal disease. Cancer stem cells (CSCs) are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterised in many cancers with data illustrating that CSCs display great abilities to self-renew, withstand therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ABC membrane transporters, activation of several survival signaling pathways and increased immune evasion DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we re-visit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.

scholarly journals Role of Claudin Proteins in Regulating Cancer Stem Cells and Chemoresistance-Potential Implication in Disease Prognosis and Therapy

2019 ◽  
Vol 21 (1) ◽  
pp. 53 ◽  
Author(s):  
Saiprasad Gowrikumar ◽  
Amar B. Singh ◽  
Punita Dhawan
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Therapy Resistance ◽  
Cell Phenotype ◽  
Potential Implication ◽  
Mesenchymal Transition ◽  
Cell Cell

Claudins are cell–cell adhesion proteins, which are expressed in tight junctions (TJs), the most common apical cell-cell adhesion. Claudin proteins help to regulate defense and barrier functions, as well as differentiation and polarity in epithelial and endothelial cells. A series of studies have now reported dysregulation of claudin proteins in cancers. However, the precise mechanisms are still not well understood. Nonetheless, studies have clearly demonstrated a causal role of multiple claudins in the regulation of epithelial to mesenchymal transition (EMT), a key feature in the acquisition of a cancer stem cell phenotype in cancer cells. In addition, claudin proteins are known to modulate therapy resistance in cancer cells, a feature associated with cancer stem cells. In this review, we have focused primarily on highlighting the causal link between claudins, cancer stem cells, and therapy resistance. We have also contemplated the significance of claudins as novel targets in improving the efficacy of cancer therapy. Overall, this review provides a much-needed understanding of the emerging role of claudin proteins in cancer malignancy and therapeutic management.

scholarly journals Pancreatic Cancer and Therapy: Role and Regulation of Cancer Stem Cells

2021 ◽  
Vol 22 (9) ◽  
pp. 4765
Author(s):  
Susmita Barman ◽  
Iram Fatima ◽  
Amar B. Singh ◽  
Punita Dhawan
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Therapeutic Approaches ◽  
Cancer Types ◽  
Pancreatic Cancer Stem Cells

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.

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