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.
Highlights
Breast cancer (BC) is a prevalent human malignancy and a very common cause of cancer-related death among women worldwide
HIF expression and transcriptional activity induced after treatment with chemotherapy in different human BC cell lines led to Breast Cancer Stem Cells (BCSCs) population enrichment through interleukin-6 (IL-6) and IL-8 signaling and MDR1 overexpression [76]
Increasing evidence indicates the existence of tumor initiating or cancer stem cells within tumors responsible in part of drug resistance and current treatment failure and recurrence
Summary
Breast cancer (BC) is a prevalent human malignancy and a very common cause of cancer-related death among women worldwide. Characterized by the overexpression and/or amplification of the human epithermal growth factor receptor 2 (HER2, known as ErbB-2, ERBB2, or HER2/neu) [3,4]. It represents the 20% of BC patients and it is associated with a more aggressive phenotype and bad prognosis [3]. Molecules 2018, 23, 2193 identified including ER+/Luminal (luminal A and B [6]), basal-like, Erb-B2+, normal like, and the claudin-low based on the gene expression pattern has emerged [7,8] This molecular classification is a complementary information for the conventional classification in tailoring treatment and predicting prognosis. Cancer Stem Cell (CSC) theory changed that idea [10]
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