Breast cancer stem cells: A review of their characteristics and the agents that affect them

Abstract

The evolving concept that cancer stem cells (CSCs) are the driving element in cancer development, evolution and heterogeneity, has overridden the previous model of a tumor consisting of cells all with similar sequentially acquired mutations and a similar potential for renewal, invasion and metastasis. This paradigm shift has focused attention on therapeutically targeting CSCs directly as a means of eradicating the disease. In breast cancers, CSCs can be identified by cell surface markers and are characterized by their ability to self-renew and differentiate, resist chemotherapy and radiation, and initiate new tumors upon serial transplantation in xenografted mice. These functional properties of CSCs are regulated by both intracellular and extracellular factors including pluripotency-related transcription factors, intracellular signaling pathways and external stimuli. Several classes of natural products and synthesized compounds have been studied to target these regulatory elements and force CSCs to lose stemness and/or terminally differentiate and thereby achieve a therapeutic effect. However, realization of an effective treatment for breast cancers, focused on the biological effects of these agents on breast CSCs, their functions and signaling, has not yet been achieved. In this review, we delineate the intrinsic and extrinsic factors identified to date that control or promote stemness in breast CSCs and provide a comprehensive compilation of potential agents that have been studied to target breast CSCs, transcription factors and stemness-related signaling. Our aim is to stimulate further study of these agents that could become the basis for their use as standalone treatments or components of combination therapies effective against breast cancers.

Ursolic Acid Decreases the Proliferation of MCF-7 Cell-Derived Breast Cancer Stem-Like Cells by Modulating the ERK and PI3K/AKT Signaling Pathways

“…Breast CSCs (BCSCs) contribute to the development of resistance to breast cancer therapy ( Zhao, 2016 ) and cancer relapse and metastasis ( Nandy and Lakshmanaswamy, 2017 ). Known BCSC markers include CD44, CD24, CD133, EpCAM, CD166, CD47, aldehyde dehydrogenase (ALDH), and ABCG2 ( Shan et al, 2021 ). Unlike in typical breast cancer, BCSCs are not a target of ER+ breast cancer endocrine therapy ( Simões et al, 2011 ), and none of the currently approved drugs for ER+ breast cancer target CSCs.…”

Collagen XVIII promotes breast cancer through EGFR/ErbB signaling and its ablation improves the efficacy of ErbB-targeting inhibitors

“…5G). Moreover, the common stem cell-related transcription factors NANOG, SNAI1, SNAI2 (SLUG) and SOX2 (29) were downregulated in the MDA-MB-231 KD cells (Fig. S7A), as also in the MCF7 cells with ColXVIII KD (Fig.…”

MicroRNA-18 facilitates the stemness of gastric cancer by downregulating HMGB3 though targeting Meis2

“…Cancer stem cells (CSCs) are proposed to be a small number of tumor cells with characteristics of stem cells and are responsible for tumor progression and initiation [ 3 ]. CSCs have complex heterogeneity and unlimited proliferation ability, which leads to tumor proliferation, metastasis, recurrence and drug resistance [ 4 ].…”