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

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.

Keywords: breast cancer stem cell-targeted strategies; breast cancer stem cells; circulating tumor cells; epithelial–mesenchymal transition; metastasis; therapy resistance.

Figure 1

An overview of the main strategies based on BCSC-targeting. After systemic application, engineered immune cells or mesenchymal stem cells (MSCs), tailored to the molecular profile of patients’ breast cancer, home in on the tumor microenvironment and release different specific anti-CSC drugs (proteins, enzymes, recombinant DNA, miRNAs, siRNAs, and chemotherapeutics). Nanoparticles containing different anti-CSC molecules can be administered alone or incorporated into MSCs to reach the tumor microenvironment and deliver drugs.