具有独特的分子表达、表面标志物、干性相关信号通路和代谢模式等方面特征的肿瘤干细胞（cancer stem cell, CSC） 因其具有高致瘤、高转移、高治疗抵抗能力，可能是多种类型恶性肿瘤生长、转移、治疗抵抗的关键因素，也是肿瘤发生和复发的 重要根源。正常干细胞在产生了第一个致癌突变之后将逐步发展成为癌前干细胞和CSC，随后在突变和微环境的共同作用下进 一步积累突变增加异质性，并与CSC可塑性转变交织在一起推动肿瘤的发生和进展，促进肿瘤的复发、转移及治疗抵抗。为了更 好地治疗肿瘤，现已研发了多种类型的靶向CSC的治疗策略，包括靶向CSC的细胞表面标志物、信号转导途径、微环境、代谢模式 等，以及促CSC分化、靶向CSC的免疫治疗等其他策略。多个靶向CSC治疗肿瘤的新药在临床试验中已经展现出良好的治疗效 果，然而，也有一些抗肿瘤新药的失败为未来研发提供了值得注意的教训。未来肿瘤治疗中，特异地靶向患者肿瘤中所有异质性 的CSC，并同时清除癌前干细胞和子代肿瘤细胞，将会更好地抑制肿瘤生长、转移和复发，从而为治愈肿瘤带来新的希望。

Cancer stem cell (CSC) is characterized by unique molecular expression, surface markers, stemness-related signaling pathways, and metabolic patterns. CSC has been the key factor for the growth, metastasis and treatment resistance in various malignancies, as well as the important reason for the tumorigenesis and recurrence due to its high tumorigenicity, metastatic potential and resistance. Normal stem cells can develop gradually into pre-cancerous stem cell (pCSC) and CSC after incurring the first oncogenic mutation. Subsequently, under the co-influence of oncogenic mutations and tumor microenvironments, oncogenic mutations are accumulated in cells, which further aiding up to tumor heterogeneity, and eventually, promote the tumorigenesis, development, relapse, metastasis, and resistance in combination with CSC plasticity transformation. In order to improve clinical outcome in tumor treatment, various therapeutic strategies targeting CSC have been developed, including cell surface markers, signal pathways, microenvironment, and metabolic patterns. Other strategies such as the promotion of CSC differentiation and immunotherapy targeting CSC are also studied. In clinical trials, several new anti-cancer drugs targeting CSC have shown favorable outcomes in patients. However, the failed attempt of some new anti-cancer drugs also holds noteworthy lessons for future development. Therefore, the specific targeting of all heterogeneous CSCs in tumor of patients and the simultaneous elimination of pCSC and progeny tumor cells will be conducive to inhibitting tumor growth, metastasis and recurrence, expecting to bring new hope for tumor therapy.

国家自然科学基金资助项目（No. 82073278）；中国医学科学院医学与健康科技创新工程项目（No. 2016-I2M-3-013）；分子肿瘤学国 家重点实验室课题项目（No. SKLMO-2021-17）