Submit to Cancers Review for Cancers Propose a Special Issue

Journal Browser

► Journal Browser

Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 June 2019) | Viewed by 101428

Share This Special Issue

Special Issue Editor

Dr. Paola Marcato

E-Mail Website
Guest Editor

Department of Pathology, Dalhousie University, Halifax, NS B3H 4G7, Canada
Interests: triple-negative breast cancer; cancer stem cells; aldehyde dehydrogenase 1A3; retinoic acid signaling; precision medicine; therapy resistance; lncRNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As with other cancers, increasing evidence supports the significance of breast cancer stem cells (CSCs) in the development and progression of breast cancer. Importantly, these cancer drivers also share many of the characteristics of stem cells, including qualities that make them resistant to commonly used cancer treatments. Mechanisms such as increased efflux capacity, higher levels of detoxifying enzymes, enhanced DNA repair, a slower cell-cycle, and increased activation of the embryonic signaling pathways (Notch, Wnt, and Hedgehog) give CSCs an increased resistance to chemotherapeutics and radiation. Clinical evidence also suggests that CSC resistance may contribute to breast tumor recurrence and poorer patient outcomes. Therefore, the development of adjuvant therapies that either target CSCs or sensitize CSCs to chemotherapies has been a major focus of recent drug discovery in the treatment of cancer. We invite original research or review articles that address the mechanisms of breast CSC therapy resistance and anti-breast CSC drug development.

Dr. Paola Marcato
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

breast cancer
cancer stem cells
therapy
resistance
recurrence

Published Papers (14 papers)

Download All Papers

Editorial

Jump to: Research, Review

5 pages, 190 KiB

Open AccessEditorial

Targeting the Roots of Recurrence: New Strategies for Eliminating Therapy-Resistant Breast Cancer Stem Cells

by Margaret L. Dahn and Paola Marcato

Cancers 2021, 13(1), 54; https://doi.org/10.3390/cancers13010054 - 28 Dec 2020

Cited by 4 | Viewed by 2367

Abstract

Cancer stem cells (CSCs) are functionally defined in our laboratories by their impressive tumor-generating and self-renewal capacity; clinically, CSCs are of interest because of their enhanced capacity to evade conventional therapies [...] Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

Research

Jump to: Editorial, Review

18 pages, 3446 KiB

Open AccessArticle

Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

by Petra Gener, Diana Rafael, Joaquin Seras-Franzoso, Anna Perez, Luis Alamo Pindado, Glòria Casas, Diego Arango, Yolanda Fernández, Zamira V. Díaz-Riascos, Ibane Abasolo and Simó Schwartz, Jr.

Cancers 2019, 11(8), 1058; https://doi.org/10.3390/cancers11081058 - 26 Jul 2019

Cited by 27 | Viewed by 4816

Abstract

Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potential. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

20 pages, 2860 KiB

Open AccessEditor’s ChoiceArticle

Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells

by Catharina Melzer, Vanessa Rehn, Yuanyuan Yang, Heike Bähre, Juliane von der Ohe and Ralf Hass

Cancers 2019, 11(6), 798; https://doi.org/10.3390/cancers11060798 - 09 Jun 2019

Cited by 171 | Viewed by 10021

Abstract

MSC-derived exosomes display, among others, an efficient biocompatibility and a reduced intrinsic immunogenicity, representing a valuable vehicle for drug delivery in a tumor-therapeutic approach. Following treatment of several human mesenchymal stroma/stem-like cell (MSC) populations with sub-lethal concentrations of taxol for 24 h, exosomes were isolated and applied to different human cancer populations including A549 lung cancer, SK-OV-3 ovarian cancer, and MDA-hyb1 breast cancer cells. While MSC control exosomes revealed little if any growth inhibition on the tumor cells, exposure to taxol-loaded MSC-derived exosomes was associated with 80–90% cytotoxicity. A similar application of taxol-loaded exosomes from HuVEC displayed much fewer effects. Quantification by LC-MS/MS analysis demonstrated a 7.6-fold reduced taxol concentration in MSC exosomes when compared to equivalent cytotoxic in vitro effects achieved with taxol substances, indicating a specific and more efficient tumor-targeting property. Consequently, MSC-derived taxol exosomes were tested in vivo. Highly metastatic MDA-hyb1 breast tumors were induced in NODscid mice, and systemic intravenous application of MSC-derived taxol exosomes revealed a more than 60% reduction of subcutaneous primary tumors. Moreover, the amount of distant organ metastases observed at least in lung, liver, spleen, and kidney was reduced by 50% with MSC taxol exosomes, similar to the effects observed with taxol, although the concentration of taxol in exosomes was about 1000-fold reduced. Together, these findings in different cancer cell populations and in vivo provide promising future perspectives for drug-loaded MSC-derived exosomes in efficiently targeting primary tumors and metastases by reducing side effects. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Graphical abstract

17 pages, 3487 KiB

Open AccessArticle

Therapeutic Potential of a Novel α_vβ₃ Antagonist to Hamper the Aggressiveness of Mesenchymal Triple Negative Breast Cancer Sub-Type

by Billy Samuel Hill, Annachiara Sarnella, Domenica Capasso, Daniela Comegna, Annarita Del Gatto, Matteo Gramanzini, Sandra Albanese, Michele Saviano, Laura Zaccaro and Antonella Zannetti

Cancers 2019, 11(2), 139; https://doi.org/10.3390/cancers11020139 - 24 Jan 2019

Cited by 33 | Viewed by 4439

Abstract

The mesenchymal sub-type of triple negative breast cancer (MES-TNBC) has a highly aggressive behavior and worse prognosis, due to its invasive and stem-like features, that correlate with metastatic dissemination and resistance to therapies. Furthermore, MES-TNBC is characterized by the expression of molecular markers related to the epithelial-to-mesenchymal transition (EMT) program and cancer stem cells (CSCs). The altered expression of α_vβ₃ integrin has been well established as a driver of cancer progression, stemness, and metastasis. Here, we showed that the high levels of α_vβ₃ are associated with MES-TNBC and therefore exploited the possibility to target this integrin to reduce the aggressiveness of this carcinoma. To this aim, MES-TNBC cells were treated with a novel peptide, named ψRGDechi, that we recently developed and characterized for its ability to selectively bind and inhibit α_vβ₃ integrin. Notably, ψRGDechi was able to hamper adhesion, migration, and invasion of MES-TNBC cells, as well as the capability of these cells to form vascular-like structures and mammospheres. In addition, this peptide reversed EMT program inhibits mesenchymal markers. These findings show that targeting α_vβ₃ integrin by ψRGDechi, it is possible to inhibit some of the malignant properties of MES-TNBC phenotype. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

26 pages, 1099 KiB

Open AccessEditor’s ChoiceReview

Breast Cancer Stem Cells as Drivers of Tumor Chemoresistance, Dormancy and Relapse: New Challenges and Therapeutic Opportunities

by Maria Laura De Angelis, Federica Francescangeli and Ann Zeuner

Cancers 2019, 11(10), 1569; https://doi.org/10.3390/cancers11101569 - 15 Oct 2019

Cited by 111 | Viewed by 7667

Abstract

Breast cancer is the most frequent cancer among women worldwide. Therapeutic strategies to prevent or treat metastatic disease are still inadequate although great progress has been made in treating early-stage breast cancer. Cancer stem-like cells (CSCs) that are endowed with high plasticity and self-renewal properties have been shown to play a key role in breast cancer development, progression, and metastasis. A subpopulation of CSCs that combines tumor-initiating capacity and a dormant/quiescent/slow cycling status is present throughout the clinical history of breast cancer patients. Dormant/quiescent/slow cycling CSCs are a key component of tumor heterogeneity and they are responsible for chemoresistance, tumor migration, and metastatic dormancy, defined as the ability of CSCs to survive in target organs and generate metastasis up to two decades after diagnosis. Understanding the strategies that are used by CSCs to resist conventional and targeted therapies, to interact with their niche, to escape immune surveillance, and finally to awaken from dormancy is of key importance to prevent and treat metastatic cancer. This review summarizes the current understanding of mechanisms involved in CSCs chemoresistance, dissemination, and metastasis in breast cancer, with a particular focus on dormant cells. Finally, we discuss how advancements in the detection, molecular understanding, and targeting of dormant CSCs will likely open new therapeutic avenues for breast cancer treatment. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

15 pages, 618 KiB

Open AccessReview

Potential Role of MSC/Cancer Cell Fusion and EMT for Breast Cancer Stem Cell Formation

by Ralf Hass, Juliane von der Ohe and Hendrik Ungefroren

Cancers 2019, 11(10), 1432; https://doi.org/10.3390/cancers11101432 - 25 Sep 2019

Cited by 45 | Viewed by 5402

Abstract

Solid tumors comprise of maturated cancer cells and self-renewing cancer stem-like cells (CSCs), which are associated with various other nontumorigenic cell populations in the tumor microenvironment. In addition to immune cells, endothelial cells, fibroblasts, and further cell types, mesenchymal stroma/stem-like cells (MSC) represent an important cell population recruited to tumor sites and predominantly interacting with the different cancer cells. Breast cancer models were among the first to reveal distinct properties of CSCs, however, the cellular process(es) through which these cells are generated, maintained, and expanded within neoplastic tissues remains incompletely understood. Here, we discuss several possible scenarios that are not mutually exclusive but may even act synergistically: fusion of cancer cells with MSC to yield hybrid cells and/or the induction of epithelial-mesenchymal transition (EMT) in breast cancer cells by MSC, which can relay signals for retrodifferentiation and eventually, the generation of breast CSCs (BCSCs). In either case, the consequences may be promotion of self-renewal capacity, tumor cell plasticity and heterogeneity, an increase in the cancer cells’ invasive and metastatic potential, and the acquisition of resistance mechanisms towards chemo- or radiotherapy. While specific signaling mechanisms involved in each of these properties remain to be elucidated, the present review article focusses on a potential involvement of cancer cell fusion and EMT in the development of breast cancer stem cells. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Graphical abstract

18 pages, 1714 KiB

Open AccessReview

Early Steps of Mammary Stem Cell Transformation by Exogenous Signals; Effects of Bisphenol Endocrine Disrupting Chemicals and Bone Morphogenetic Proteins

by Nora Jung, Veronique Maguer-Satta and Boris Guyot

Cancers 2019, 11(9), 1351; https://doi.org/10.3390/cancers11091351 - 12 Sep 2019

Cited by 8 | Viewed by 3607

Abstract

Estrogens are major regulators of the mammary gland development, notably during puberty, via estrogen receptor (ER) activation, leading to the proliferation and differentiation of mammary cells. In addition to estrogens, the bone morphogenetic proteins (BMPs) family is involved in breast stem cell/progenitor commitment. However, these two pathways that synergistically contribute to the biology of the normal mammary gland have also been described to initiate and/or promote breast cancer development. In addition to intrinsic events, lifestyle habits and exposure to environmental cues are key risk factors for cancer in general, and especially for breast cancer. In the latter case, bisphenol A (BPA), an estrogen-mimetic compound, is a critical pollutant both in terms of the quantities released in our environment and of its known and speculated effects on mammary gland biology. In this review, we summarize the current knowledge on the actions of BMPs and estrogens in both normal mammary gland development and breast cancer initiation, dissemination, and resistance to treatment, focusing on the dysregulations of these processes by BPA but also by other bisphenols, including BPS and BPF, initially considered as safer alternatives to BPA. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

36 pages, 2366 KiB

Open AccessEditor’s ChoiceReview

Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness

by Kha-Liang Lee, Yung-Che Kuo, Yuan-Soon Ho and Yen-Hua Huang

Cancers 2019, 11(9), 1334; https://doi.org/10.3390/cancers11091334 - 09 Sep 2019

Cited by 147 | Viewed by 17706

Abstract

Triple-negative breast cancer (TNBC) is cancer that tested as negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein which accounts for 15%–20% of all breast cancer cases. TNBC is considered to be a poorer prognosis than other types of breast cancer, mainly because it involves more aggressive phenotypes that are similar to stem cell–like cancer cells (cancer stem cell, CSC). Thus, targeted treatment of TNBC remains a major challenge in clinical practice. This review article surveys the latest evidence concerning the role of genomic alteration in current TNBC treatment responses, current clinical trials and potential targeting sites, CSC and drug resistance, and potential strategies targeting CSCs in TNBC. Furthermore, the role of insulin-like growth factor 1 receptor (IGF-1R) and nicotinic acetylcholine receptors (nAChR) in stemness expression, chemoresistance, and metastasis in TNBC and their relevance to potential treatments are also discussed and highlighted. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

22 pages, 818 KiB

Open AccessFeature PaperReview

Role of the Microenvironment in Regulating Normal and Cancer Stem Cell Activity: Implications for Breast Cancer Progression and Therapy Response

by Vasudeva Bhat, Alison L. Allan and Afshin Raouf

Cancers 2019, 11(9), 1240; https://doi.org/10.3390/cancers11091240 - 24 Aug 2019

Cited by 25 | Viewed by 5808

Abstract

The epithelial cells in an adult woman’s breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment. However, current evidence suggests that alterations to the communication between MaSCs, epithelial progenitors and their microenvironment plays an important role in breast carcinogenesis. In this article, we review the current knowledge regarding the role of the breast tissue microenvironment in regulating the special functions of normal and cancer stem cells. Understanding the crosstalk between MaSCs and their microenvironment will provide new insights into how an altered breast tissue microenvironment could contribute to breast cancer development, progression and therapy response and the implications of this for the development of novel therapeutic strategies to target cancer stem cells. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

20 pages, 5358 KiB

Open AccessReview

SETDB-1: A Potential Epigenetic Regulator in Breast Cancer Metastasis

by Jacob Batham, Pek Siew Lim and Sudha Rao

Cancers 2019, 11(8), 1143; https://doi.org/10.3390/cancers11081143 - 09 Aug 2019

Cited by 24 | Viewed by 7305

Abstract

The full epigenetic repertoire governing breast cancer metastasis is not completely understood. Here, we discuss the histone methyltransferase SET Domain Bifurcated Histone Lysine Methyltransferase 1 (SETDB1) and its role in breast cancer metastasis. SETDB1 serves as an exemplar of the difficulties faced when developing therapies that not only specifically target cancer cells but also the more elusive and aggressive stem cells that contribute to metastasis via epithelial-to-mesenchymal transition and confer resistance to therapies. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

21 pages, 699 KiB

Open AccessReview

CSCs in Breast Cancer—One Size Does Not Fit All: Therapeutic Advances in Targeting Heterogeneous Epithelial and Mesenchymal CSCs

by Andrew Sulaiman, Sarah McGarry, Xianghui Han, Sheng Liu and Lisheng Wang

Cancers 2019, 11(8), 1128; https://doi.org/10.3390/cancers11081128 - 07 Aug 2019

Cited by 27 | Viewed by 5408

Abstract

Unlike other breast cancer subtypes, triple-negative breast cancer (TNBC) has no specific targets and is characterized as one of the most aggressive subtypes of breast cancer that disproportionately accounts for the majority of breast cancer-related deaths. Current conventional chemotherapeutics target the bulk tumor population, but not the cancer stem cells (CSCs) that are capable of initiating new tumors to cause disease relapse. Recent studies have identified distinct epithelial-like (E) ALDH⁺ CSCs, mesenchymal-like (M) CD44⁺/CD24⁻ CSCs, and hybrid E/M ALDH⁺/CD44⁺/CD24⁻ CSCs. These subtypes of CSCs exhibit differential signal pathway regulations, possess plasticity, and respond differently to treatment. As such, co-inhibition of different subtypes of CSCs is key to viable therapy. This review serves to highlight different pathway regulations in E and M CSCs in TNBC, and to further describe their role in disease progression. Potential inhibitors targeting E and/or M CSCs based on clinical trials are summarized for further investigation. Since future research needs to adopt suitable tumor models and take into account the divergence of E and M CSCs for the development of effective treatments, TNBC models for clinically translatable studies are further discussed. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

28 pages, 1438 KiB

Open AccessReview

The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer

by David Rodriguez, Marc Ramkairsingh, Xiaozeng Lin, Anil Kapoor, Pierre Major and Damu Tang

Cancers 2019, 11(7), 1028; https://doi.org/10.3390/cancers11071028 - 22 Jul 2019

Cited by 51 | Viewed by 6352

Abstract

Breast cancer stem cells (BCSC) play critical roles in the acquisition of resistance to endocrine therapy in estrogen receptor (ER)-positive (ER + ve) breast cancer (BC). The resistance results from complex alterations involving ER, growth factor receptors, NOTCH, Wnt/β-catenin, hedgehog, YAP/TAZ, and the tumor microenvironment. These mechanisms are likely converged on regulating BCSCs, which then drive the development of endocrine therapy resistance. In this regard, hormone therapies enrich BCSCs in ER + ve BCs under both pre-clinical and clinical settings along with upregulation of the core components of “stemness” transcriptional factors including SOX2, NANOG, and OCT4. SOX2 initiates a set of reactions involving SOX9, Wnt, FXY3D, and Src tyrosine kinase; these reactions stimulate BCSCs and contribute to endocrine resistance. The central contributions of BCSCs to endocrine resistance regulated by complex mechanisms offer a unified strategy to counter the resistance. ER + ve BCs constitute approximately 75% of BCs to which hormone therapy is the major therapeutic approach. Likewise, resistance to endocrine therapy remains the major challenge in the management of patients with ER + ve BC. In this review we will discuss evidence supporting a central role of BCSCs in developing endocrine resistance and outline the strategy of targeting BCSCs to reduce hormone therapy resistance. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

29 pages, 843 KiB

Open AccessReview

The Role of Breast Cancer Stem Cells as a Prognostic Marker and a Target to Improve the Efficacy of Breast Cancer Therapy

by Maria Giovanna Scioli, Gabriele Storti, Federico D’Amico, Pietro Gentile, Giulia Fabbri, Valerio Cervelli and Augusto Orlandi

Cancers 2019, 11(7), 1021; https://doi.org/10.3390/cancers11071021 - 20 Jul 2019

Cited by 50 | Viewed by 7860

Abstract

Breast cancer is the most common form of tumor in women and the leading cause of cancer-related mortality. Even though the major cellular burden in breast cancer is constituted by the so-called bulk tumor cells, another cell subpopulation named cancer stem cells (CSCs) has been identified. The latter have stem features, a self-renewal capacity, and the ability to regenerate the bulk tumor cells. CSCs have been described in several cancer types but breast cancer stem cells (BCSCs) were among the first to be identified and characterized. Therefore, many efforts have been put into the phenotypic characterization of BCSCs and the study of their potential as prognostic indicators and therapeutic targets. Many dysregulated pathways in BCSCs are involved in the epithelial–mesenchymal transition (EMT) and are found up-regulated in circulating tumor cells (CTCs), another important cancer cell subpopulation, that shed into the vasculature and disseminate along the body to give metastases. Conventional therapies fail at eliminating BCSCs because of their quiescent state that gives them therapy resistance. Based on this evidence, preclinical studies and clinical trials have tried to establish novel therapeutic regimens aiming to eradicate BCSCs. Markers useful for BCSC identification could also be possible therapeutic methods against BCSCs. New approaches in drug delivery combined with gene targeting, immunomodulatory, and cell-based therapies could be promising tools for developing effective CSC-targeted drugs against breast cancer. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Figure 1

30 pages, 1880 KiB

Open AccessEditor’s ChoiceReview

Targeting Cancer Stem Cells in Triple-Negative Breast Cancer

by So-Yeon Park, Jang-Hyun Choi and Jeong-Seok Nam

Cancers 2019, 11(7), 965; https://doi.org/10.3390/cancers11070965 - 09 Jul 2019

Cited by 113 | Viewed by 11723

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that lacks targeted therapy options, and patients diagnosed with TNBC have poorer outcomes than patients with other breast cancer subtypes. Emerging evidence suggests that breast cancer stem cells (BCSCs), which have tumor-initiating potential and possess self-renewal capacity, may be responsible for this poor outcome by promoting therapy resistance, metastasis, and recurrence. TNBC cells have been consistently reported to display cancer stem cell (CSC) signatures at functional, molecular, and transcriptional levels. In recent decades, CSC-targeting strategies have shown therapeutic effects on TNBC in multiple preclinical studies, and some of these strategies are currently being evaluated in clinical trials. Therefore, understanding CSC biology in TNBC has the potential to guide the discovery of novel therapeutic agents in the future. In this review, we focus on the self-renewal signaling pathways (SRSPs) that are aberrantly activated in TNBC cells and discuss the specific signaling components that are involved in the tumor-initiating potential of TNBC cells. Additionally, we describe the molecular mechanisms shared by both TNBC cells and CSCs, including metabolic plasticity, which enables TNBC cells to switch between metabolic pathways according to substrate availability to meet the energetic and biosynthetic demands for rapid growth and survival under harsh conditions. We highlight CSCs as potential key regulators driving the aggressiveness of TNBC. Thus, the manipulation of CSCs in TNBC can be a targeted therapeutic strategy for TNBC in the future. Full article

(This article belongs to the Special Issue Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Breast Cancer Stem Cells: Therapy Resistance and Novel Therapeutic Targets

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (14 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI