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Review
. 2018 Aug 30;23(9):2193.
doi: 10.3390/molecules23092193.

Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance

Sònia Palomeras  1 , Santiago Ruiz-Martínez  2 , Teresa Puig  3
Affiliations
Review

Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance

Sònia Palomeras et al. Molecules. .

Abstract

Despite advances in breast cancer diagnosis and treatment, many patients still fail therapy, resulting in disease progression, recurrence, and reduced overall survival. Historically, much focus has been put on the intrinsic subtyping based in the presence (or absence) of classical immunohistochemistry (IHC) markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-related protein (HER2). However, it is widely understood that tumors are composed of heterogeneous populations of cells with a hierarchical organization driven by cancer stem cells (CSCs). In breast tumors, this small population of cells displaying stem cell properties is known as breast CSCs (BCSCs). This rare population exhibit a CD44⁺/CD24-/low phenotype with high ALDH activity (ALDH⁺), and possesses higher tolerability to chemotherapy, hormone therapy, and radiotherapy and is able to reproduce the bulk of the tumor after reduction of cell populations sensitive to first-line therapy leading to disease relapse. In this review, we present special attention to BCSCs with future directions in the establishment of a therapy targeting this population. Drugs targeting the main BCSCs signaling pathways undergoing clinical trials are also summarized.

Keywords: BCSCs; BCSCs markers; breast cancer; resistance; targeted therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of tumor cell heterogeneity in an aggressive breast cancer. The primary tumor is formed of heterogeneous subpopulations of cells including breast cancer stem cells (BCSCs). Usually, a first-line therapy is chosen based on the histological subtype, stage of the tumor, presence of biomarkers, and other clinical data. If the first-line therapy does not target BCSCs, the mass of the tumor will be reduced but BCSCs will remain (mostly) unaffected. BCSCs present in the primary tumor can expand and give rise to a multi-drug resistant tumor (secondary breast tumor), leading to progression and metastasis of the tumor.
Figure 2
Figure 2
Summary of breast cancer stem cells (BCSCs) characteristics.
Figure 3
Figure 3
Schematic representation of the main BCSC signaling pathways, Notch, Wnt (canonical and non-canonical), and Hedgehog (Hh). Some of the current drugs in clinical trials directed to BCSC pathways are indicated. GSIs: γ-secretase inhibitors (MK-0752, RO4929097, and PF-03084014).
See this image and copyright information in PMC

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