Hua Zhan, White Jason, Zhou Jianjun
Department of General Surgery, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.
Tuskegee University, Center for Cancer Research, Tuskegee, AL, 36830, USA.
Semin Cancer Biol. 2022 Jul;82:26-34. doi: 10.1016/j.semcancer.2021.06.015. Epub 2021 Jun 18.
Triple-negative breast cancer (TNBC) is a broad collection of breast cancer that tests negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein. TNBC is considered to have poorer prognosis than other types of breast cancer because of a lack of effective therapeutic targets. The success of precision cancer therapies relies on the clarification of key molecular mechanisms that drive tumor growth and metastasis; however, TNBC is highly heterogeneous in terms of their cellular lineage composition and the molecular nature within each individual case. In particular, the rare and sometimes slow cycling cancer stem cells (CSCs) can provide effective means for TNBC to resist various treatments. Single cell analysis technologies, including single-cell RNA-seq (scRNA-seq) and proteomics, provide an avenue to unravel patient-level intratumoral heterogeneity by identifying CSCs populations, CSC biomarkers and the range of tumor microenvironment cellular constituents that contribute to tumor growth. This review discusses the emerging evidence for the role of CSCs in driving TNBC incidence and the therapeutic implications in manipulating molecular signaling against this rare cell population for the control of this deadly disease.
三阴性乳腺癌(TNBC)是一类广泛的乳腺癌,其雌激素受体(ER)、孕激素受体(PR)以及过量的人表皮生长因子受体2(HER2)蛋白检测均为阴性。由于缺乏有效的治疗靶点,TNBC被认为比其他类型的乳腺癌预后更差。精准癌症治疗的成功依赖于对驱动肿瘤生长和转移的关键分子机制的阐明;然而,TNBC在细胞谱系组成和每个病例的分子特性方面具有高度的异质性。特别是,罕见且有时处于缓慢循环状态的癌症干细胞(CSC)可为TNBC抵抗各种治疗提供有效途径。单细胞分析技术,包括单细胞RNA测序(scRNA-seq)和蛋白质组学,通过识别CSC群体、CSC生物标志物以及有助于肿瘤生长的肿瘤微环境细胞成分范围,为揭示患者水平的肿瘤内异质性提供了一条途径。本综述讨论了CSC在驱动TNBC发病中的作用的新证据,以及针对这一罕见细胞群体操纵分子信号以控制这种致命疾病的治疗意义。