Mao Xiao-Dong, Wei Xiao, Xu Tao, Li Tai-Ping, Liu Kang-Sheng
Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine Nanjing 210028, Jiangsu, China.
Key Laboratory of TCM Syndrome & Treatment of Yingbing of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine Nanjing 210028, Jiangsu, China.
Am J Cancer Res. 2022 Jul 15;12(7):3208-3222. eCollection 2022.
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.
越来越多的研究证明，乳腺肿瘤中存在少量具有自我更新和分化能力的细胞，即乳腺癌干细胞。这类细胞在乳腺肿瘤的起始、发展和转移中起关键作用。乳腺癌干细胞的特性受一系列细胞内和细胞外因素调控，包括重要的信号通路、转录因子、非编码RNA以及细胞因子，如刺猬因子（Hedgehog）、Wnt、Notch、微小RNA93（microRNA93）、微小RNA100（microRNA100）和白细胞介素-6（IL-6）。肿瘤微环境（如间充质干细胞、巨噬细胞和细胞因子）在乳腺癌干细胞的调控中起重要作用。本研究使用“乳腺癌干细胞”“信号通路”“化疗耐受性”“非编码RNA”“三阴性乳腺癌”“抑制剂”等关键词，从PubMed和科学网（WEB OF SCI）数据库检索了2021年10月3日前发表的原始文章和综述，并对其进行了全面综述。治疗后，乳腺癌干细胞的易转移特性与复发之间存在相关性。乳腺癌干细胞的信号通路在激活乳腺癌细胞功能、调节乳腺癌细胞分化和控制乳腺癌细胞分裂中起重要作用。这种失衡导致乳腺癌细胞不受控制地生长和发展。阻断相应通路的靶向治疗可能成为乳腺癌治疗的新视角。此外，可根据不同分子类型乳腺癌干细胞的表达特征采用相应的治疗策略。对于雌激素受体（ER）阳性的乳腺癌，同时进行内分泌治疗和肿瘤干细胞靶向治疗可能提高内分泌治疗的疗效。曲妥珠单抗治疗可显著降低人表皮生长因子受体2（HER2）阳性乳腺癌的复发风险。对于耐药患者，由于上皮-间质转化肿瘤干细胞的表型不同，需要联合治疗。本研究简要综述了乳腺癌干细胞相关信号通路及其抑制剂的研究进展，以便为乳腺癌患者获得更有效的临床治疗提供参考。
