Cancer stem cells (CSCs) are a small subpopulation of tumor cells critical for tumor development. Their unique abilities, such as self-renewal, have resulted in tumor resistance to various cancer treatments, including traditional chemotherapy and latest immunotherapy. CSCs-targeting therapy is a promising treatment to overcome the therapeutic resistances to different tumors. However, despite their significance, the regulatory mechanism generating therapy-resistant CSCs is still obscure. Long non-coding RNAs (lncRNAs) are key regulators in various biological processes, including cell proliferation, apoptosis, migration, and invasion. Recent studies have revealed that lncRNAs play an important role in the therapeutic resistance of CSCs. Here we summarize the latest studies on the regulatory role of lncRNAs in sustaining the stemness of CSCs, and discuss the associated mechanisms behind these behavior changes in CSCs-related chemo- and immune-resistance. Future research implications are also discussed, shedding light on the potential CSCs-targeted strategies to break through the resistance of current therapies.

癌症干细胞（CSC）是一小部分肿瘤细胞，对于肿瘤的发展至关重要。它们的独特能力，例如自我更新，已导致肿瘤对包括传统化学疗法和最新免疫疗法在内的各种癌症治疗产生了抵抗力。CSCs靶向治疗是克服对不同肿瘤的治疗抗性的一种有前途的治疗方法。然而，尽管具有重要意义，但产生抗药性CSC的调节机制仍然不清楚。长非编码RNA（lncRNA）是各种生物学过程（包括细胞增殖，凋亡，迁移和侵袭）中的关键调控因子。最近的研究表明，lncRNA在CSC的治疗耐药性中起重要作用。在这里，我们总结了有关lncRNA在维持CSC的干性中的调控作用的最新研究，并讨论了这些行为改变与CSCs相关的化学和免疫抵抗的相关机制。还讨论了未来的研究意义，阐明了潜在的针对CSCs的策略，以突破当前疗法的耐药性。