Abstract

Breast cancer is the most common malignancy affecting women worldwide. Importantly, there have been significant improvements in prevention, early diagnosis, and treatment options, which resulted in a significant decrease in breast cancer mortality rates. Nevertheless, the high rates of incidence combined with therapy resistance result in cancer relapse and metastasis, which still contributes to unacceptably high mortality of breast cancer patients. In this context, a small subpopulation of highly tumourigenic cancer cells within the tumour bulk, commonly designated as breast cancer stem cells (BCSCs), have been suggested as key elements in therapy resistance, which are responsible for breast cancer relapses and distant metastasis. Thus, improvements in BCSC-targeting therapies are crucial to tackling the metastatic progression and might allow therapy resistance to be overcome. However, the design of effective and specific BCSC-targeting therapies has been challenging since there is a lack of specific biomarkers for BCSCs, and the most common clinical approaches are designed for commonly altered BCSCs signalling pathways. Therefore, the search for a new class of BCSC biomarkers, such as the expression of membrane proteins with cancer stem cell potential, is an area of clinical relevance, once membrane proteins are accessible on the cell surface and easily recognized by specific antibodies. Here, we discuss the significance of BCSC membrane biomarkers as potential prognostic and therapeutic targets, reviewing the CSC-targeting therapies under clinical trials for breast cancer.

Highlights

  • Upon cancer stem cells (CSCs) first identification in leukaemia, in 1994 [1], many studies intended to unravel their key traits and mechanisms in cancer biology

  • Our group has recently demonstrated that breast cancer cells that have in vivo metastatic capacity in mice models [41] have increased CSC activity, but most importantly, we showed that human metastatic lesions [42], brain metastasis, are enriched for a breast cancer stem cells (BCSCs) phenotype

  • There are no universal markers that allow the specific recognition of BCSCs, this population is generally identified by the expression of the surface markers CD44, CD24, and ALDH1, which are the most accepted biomarkers associated with a BCSC phenotype

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Summary

Introduction

Upon cancer stem cells (CSCs) first identification in leukaemia, in 1994 [1], many studies intended to unravel their key traits and mechanisms in cancer biology. Over the years, increasing evidence has revealed a role for these highly tumourigenic cancer cells in cancer progression and metastasis [2]

Cancer Stem Cells’ Biology and Their Role in Metastasis
Cancer Stem Cells’ Resistance to Therapy
Main features ofself-renewal
BCSC Biomarkers
Transcription Factors (TFs)
Cell Surface Proteins
Clinical Relevance of BCSC Biomarkers
Breast
Targeting BCSC Signalling Pathways
Hh Signalling
Wnt Signalling
Targeting BCSCs’ Cell Surface Membrane Biomarkers
CD44v6
Epithelial Cell Adhesion Molecule (EpCAM)
Cadherin-3 (P-Cadherin)
Erb-b2 Receptor Tyrosine Kinase 2 (Erbb2/HER2)
C–X–C Motif Chemokine Receptor 1 (CXCR1)
Findings
Conclusions

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