Chemoresistance in Cancer Stem Cells and Strategies to Overcome Resistance

Thomas, Margaret Lois; Coyle, Krysta M.; Sultan, Mohammad; Vaghar-Kashani, Ahmad; Marcato, Paola

doi:10.4172/2167-7700.1000125

Cited by 10 publications

(6 citation statements)

References 151 publications

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“…Of the breast cancer subtypes, TNBC/basal-like breast cancers have higher percentages of CSCs, which may contribute to their aggressiveness and the worse patient outcomes associated with these breast cancers (17)(18)(19)(20)(21)(22)(23). In terms of mitigating the risk of recurrence, the resistance of CSCs to chemotherapies, radiotherapy, and possibly immunotherapies is an increasing concern (24)(25)(26)(27)(28)(29). Therapies that target CSCs may reduce the risk of relapse.…”

Section: Breast Cancer Stem Cells: Inherent Metabolic Plasticitymentioning

confidence: 99%

The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

et al. 2019

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Within heterogeneous tumors, cancer stem cell (CSC) populations exhibit the greatest tumor initiation potential, promote metastasis, and contribute to therapy resistance. For breast cancer specifically, CSCs are identified by CD44 high CD24 low cell surface marker expression and increased aldehyde dehydrogenase activity. In general, bulk breast tumor cells possess altered energetics characterized by aerobic glycolysis. In contrast, breast CSCs appear to have adaptive metabolic plasticity that allows these tumor-initiating cells to switch between glycolysis and oxidative phosphorylation, depending on factors present in the tumor microenvironment (e.g., hypoxia, reactive oxygen species, availability of glucose). In this article, we review the regulatory molecules that may facilitate the metabolic plasticity of breast CSCs. These regulatory factors include epigenetic chromatin modifiers, non-coding RNAs, transcriptional repressors, transcription factors, energy and stress sensors, and metabolic enzymes. Furthermore, breast cancer cells acquire CSC-like characteristics and altered energetics by undergoing epithelial-mesenchymal transition (EMT). This energy costly process is paired with reprogrammed glucose metabolism by epigenetic modifiers that regulate expression of both EMT and other metabolism-regulating genes. The survival advantage imparted to breast CSCs by metabolic plasticity suggests that targeting the factors that mediate the energetic switch should hinder tumorigenesis and lead to improved patient outcomes.

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Section: Breast Cancer Stem Cells: Inherent Metabolic Plasticitymentioning

confidence: 99%

The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

et al. 2019

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“…Within tumors, CSCs are the most tumorigenic cells, initiating new tumors with high efficiency [15]. Most concerning in terms of mitigating the risk of metastasis and recurrence in the treatment of TNBC/basal-like breast cancers is the resistance of CSCs to chemotherapies [16].…”

mentioning

confidence: 99%

“…Given the high abundance of CSCs within TNBC/basal-like breast cancer, novel therapies that also target CSCs may better reduce the risk of relapse and improve the outcomes of TNBC patients. Components of dysregulated CSC-enriched molecular pathways (e.g., Notch, Wnt, and Hh) may exemplify novel druggable targets for signaling antagonists [16,39,40]. Additionally, increasing evidence suggests that it may be possible to target CSCs via CSC-specific or associated non-coding RNAs [41][42][43][44].…”

mentioning

confidence: 99%

The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

Brown

Wasson

Marcato

2020

Cells

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Treatment decisions for breast cancer are based on staging and hormone receptor expression and include chemotherapies and endocrine therapy. While effective in many cases, some breast cancers are resistant to therapy, metastasize and recur, leading to eventual death. Higher percentages of tumor-initiating cancer stem cells (CSCs) may contribute to the increased aggressiveness, chemoresistance, and worse outcomes among breast cancer. This may be particularly true in triple-negative breast cancers (TNBCs) which have higher percentages of CSCs and are associated with worse outcomes. In recent years, increasing numbers of long non-coding RNAs (lncRNAs) have been identified as playing an important role in breast cancer progression and some of these have been specifically associated within the CSC populations of breast cancers. LncRNAs are non-protein-coding transcripts greater than 200 nucleotides which can have critical functions in gene expression regulation. The preclinical evidence regarding lncRNA antagonists for the treatment of cancer is promising and therefore, presents a potential novel approach for treating breast cancer and targeting therapy-resistant CSCs within these tumors. Herein, we summarize the lncRNAs that have been identified as functionally relevant in breast CSCs. Furthermore, our review of the literature and analysis of patient datasets has revealed that many of these breast CSC-associated lncRNAs are also enriched in TNBC. Together, this suggests that these lncRNAs may be playing a particularly important role in TNBC. Thus, certain breast cancer-promoting/CSC-associated lncRNAs could be targeted in the treatment of TNBCs and the CSCs within these tumors should be susceptible to anti-lncRNA therapy.

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“…MDR of CSCs is based on many cellular activities, such as the DNA repair system, transporter efflux pump, detoxification enzymes (aldehyde dehydrogenase, DNA topoisomerase, protein kinase C, dihydrofolate reductase, glutathione and glutathione S-transferases [GST]), EMT, autophagy, oncogenes (EGFR, PI3K/AKT, ERK, and NF-кB), microRNAs, tumor suppressor genes (e.g., p53), and B-cell lymphoma 2 (Bcl-2). In addition, microenvironmental conditions, such as hypoxia, pH, and paracrine signals, affect the drug-resistance capacity of CSCs [78][79][80][81][82][83] . Protein activity plays a role in the form of efflux pumps that excrete a broad range of chemotherapeutic drugs (e.g., doxorubicin [DOX], cisplatin, 5fluorouracil [5-FU], colchicine, methotrexate, etoposide) out of CSCs, thereby preventing their cytotoxicity and supporting the chemoresistance of CSCs 82 .…”

Section: Mechanisms Of Mdr In Cscsmentioning

confidence: 99%

The relationship between autophagy and multidrug resistance in cancer stem cells

2022

Sci. Tech. Dev. J.

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Cancer stem cells (CSCs) are considered the origin of tumors and cancer. Recently, CSCs have been described as the cause of multidrug resistance (MDR) in almost all cancers. The MDR phenotype of CSCs manifests as the upregulation of ATP-binding cassette subfamily G, isoform 2 protein (ABCG2) in the cell membranes of CSCs. However, recent studies have demonstrated a relationship between MDR and the autophagy process of CSCs. Based on publications indexed in PubMed, Google Scholar, and Scopus, this review summarizes the relationship between autophagy and MDR in CSCs and the approaches to targeting autophagy to reduce MDR in CSCs. Autophagy can be considered a new target to overcome MDR in cancer treatment.

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Chemoresistance in Cancer Stem Cells and Strategies to Overcome Resistance

Cited by 10 publications

References 151 publications

The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

The relationship between autophagy and multidrug resistance in cancer stem cells

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