Research progress in breast cancer stem cells: characterization and future perspectives

Am J Cancer Res. 2022 Jul 15;12(7):3208-3222. eCollection 2022.

Abstract

More and more studies have proved that there are a small number of cells with self-renewal and differentiation ability in breast tumors, namely breast cancer stem cells. Such cells play a key role in the initiation, development and migration of breast tumors. The properties of breast tumor stem cells are regulated by a range of intracellular and extracellular factors, including important signaling pathways, transcription factors, non-coding RNAs, and cytokines such as Hedgehog, Wnt, Notch, microRNA93, microRNA100, and IL-6. Tumor microenvironment (such as mesenchymal stem cells, macrophages and cytokines) plays an important role in the regulation of breast tumor stem cells. Using the keywords including "breast cancer stem cells", "signal pathway", "chemotherapy tolerance", and "non-coding RNA", "triple negative breast cancer", "inhibitors", this study retrieved the original articles and reviews published before October 3, 2021, from PubMed and WEB OF SCI database and this study performed a comprehensive review of them. After treatment, there is a correlation between the metastasis-prone nature and recurrence with breast cancer stem cells. The signaling pathway of breast cancer stem cells plays a significant role in activating the function of breast cancer cells, regulating the differentiation of breast cancer cells and controlling the division of breast cancer cells. This imbalance leads to the uncontrolled growth and development of breast cancer cells. Targeted therapy that blocks the corresponding pathway may become a new perspective for breast cancer treatment. In addition, corresponding therapeutic strategies can be used according to the expression characteristics of different molecular types of breast cancer stem cells. For ER-positive breast cancer, simultaneous endocrine therapy and targeted therapy of tumor stem cells may improve the efficacy of endocrine therapy. Trastuzumab therapy significantly reduces the risk of recurrence of HER2-positive breast cancer. For drug-resistant patients, combination therapy is required due to the different phenotypes of epithelial-mesenchymal transforming tumor stem cells. This study briefly reviews the research progress of breast cancer stem cell-related signaling pathways and their inhibitors, in order to provide a reference for breast cancer patients to obtain more effective clinical treatment.

Keywords: Breast cancer stem cells; HER2 positive breast cancer; chemotherapy tolerance; inhibitors; regulating cell differentiation; signal pathway; triple negative breast cancer.

Publication types

  • Review