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Review
. 2019 Aug 18;8(8):926.
doi: 10.3390/cells8080926.

Cancer Stem Cells and Targeting Strategies

Luisa Barbato  1 , Marco Bocchetti  1   2 , Anna Di Biase  1 , Tarik Regad  3
Affiliations
Review

Cancer Stem Cells and Targeting Strategies

Luisa Barbato et al. Cells. .

Abstract

Chemoresistance is a major problem in cancer therapy as cancer cells develop mechanisms that counteract the effect of chemotherapeutic compounds, leading to relapse and the development of more aggressive cancers that contribute to poor prognosis and survival rates of treated patients. Cancer stem cells (CSCs) play a key role in this event. Apart from their slow proliferative property, CSCs have developed a range of cellular processes that involve drug efflux, drug enzymatic inactivation and other mechanisms. In addition, the microenvironment where CSCs evolve (CSC niche), effectively contributes to their role in cancer initiation, progression and chemoresistance. In the CSC niche, immune cells, mesenchymal stem cells (MSCs), endothelial cells and cancer associated fibroblasts (CAFs) contribute to the maintenance of CSC malignancy via the secretion of factors that promote cancer progression and resistance to chemotherapy. Due to these factors that hinder successful cancer therapies, CSCs are a subject of intense research that aims at better understanding of CSC behaviour and at developing efficient targeting therapies. In this review, we provide an overview of cancer stem cells, their role in cancer initiation, progression and chemoresistance, and discuss the progress that has been made in the development of CSC targeted therapies.

Keywords: cancer; cancer stem cells (CSCs); chemoresistance; chemotherapy; microenvironment; therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of cancer stem cells (CSCs) and their role in chemoresistance. (A) Chemotherapy destroys most of the highly proliferative cancer cells. CSCs are less affected by chemotherapy and can re-initiate cancer and promote cancer progression. (B) CSCs possess several mechanisms that counteract the effect of chemotherapeutic compounds such as the ATP family of transporters, higher expression of the pro-survival factor BCL2 (B-cell lymphoma 2), higher expression of the detoxifying enzymes aldehyde dehydrogenases (ALDHs), a more efficient DNA damage response and a slower rate of cell division or dormancy.
Figure 2
Figure 2
Schematic representation of the CSC microenvironment (CSC niche). The complex CSC niche contains several cell types including mesenchymal stem cells (MSCs), endothelial cells, cancer associated fibroblasts (CAFs) and immune cells (tumour associated macrophages (TAMs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and T-helper cells (Th17)). These cells secrete different cytokines and growth factors that promote tumourigenesis, tumour progression and immunosuppression.
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