Jia Haiqing, Wei Jing, Zheng Wei, Li Zhuo
Department of Gynecology, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, No.44 xiaoheyan road, Shenyang, 110042, China.
J Transl Med. 2025 May 25;23(1):583. doi: 10.1186/s12967-025-06595-z.
Cancer stem cells (CSCs) constitute a small yet crucial subgroup in tumors, known for their capacity to self-renew, differentiate, and promote tumor growth, metastasis, and resistance to therapy. These characteristics position CSCs as significant factors in tumor recurrence and unfavorable clinical results, emphasizing their role as targets for therapy. Autophagy, an evolutionarily preserved cellular mechanism for degradation and recycling, has a complex function in cancer by aiding cell survival during stress and preserving balance by eliminating damaged organelles and proteins. Although autophagy can hinder tumor growth by reducing genomic instability, it also aids tumor advancement, particularly in harsh microenvironments, highlighting its dual characteristics. Recent research has highlighted the complex interactions between autophagy and CSCs, showing that autophagy governs CSC maintenance, boosts survival, and aids in resistance to chemotherapy and radiotherapy. On the other hand, in specific situations, autophagy may restrict CSC growth by increasing differentiation or inducing cell death. These intricate interactions offer both obstacles and possibilities for therapeutic intervention. Pharmacological modulation of autophagy, via inhibitors like chloroquine or by enhancing autophagy when advantageous, has demonstrated potential in making CSCs more responsive to standard treatments. Nonetheless, applying these strategies in clinical settings necessitates a better understanding of context-dependent autophagy dynamics and the discovery of dependable biomarkers indicating autophagic activity in CSCs. Progressing in this area might unveil novel, accurate strategies to tackle therapy resistance, lessen tumor recurrence, and ultimately enhance patient outcomes.
癌症干细胞(CSCs)是肿瘤中一个虽小但至关重要的亚群,以其自我更新、分化以及促进肿瘤生长、转移和治疗抵抗的能力而闻名。这些特性使癌症干细胞成为肿瘤复发和不良临床结果的重要因素,凸显了它们作为治疗靶点的作用。自噬是一种进化上保守的细胞降解和再循环机制,在癌症中具有复杂的功能,它通过在应激期间帮助细胞存活以及通过清除受损细胞器和蛋白质来维持平衡。尽管自噬可以通过减少基因组不稳定性来阻碍肿瘤生长,但它也有助于肿瘤进展,特别是在恶劣的微环境中,这凸显了其双重特性。最近的研究突出了自噬与癌症干细胞之间的复杂相互作用,表明自噬控制癌症干细胞的维持、提高存活率并有助于抵抗化疗和放疗。另一方面,在特定情况下,自噬可能通过增加分化或诱导细胞死亡来限制癌症干细胞的生长。这些复杂的相互作用为治疗干预既带来了障碍也提供了可能性。通过使用氯喹等抑制剂或在有利时增强自噬对自噬进行药理学调节,已显示出使癌症干细胞对标准治疗更敏感的潜力。然而,在临床环境中应用这些策略需要更好地理解依赖于背景的自噬动态,并发现可靠的生物标志物来指示癌症干细胞中的自噬活性。在这一领域取得进展可能会揭示新颖、准确的策略来解决治疗抵抗、减少肿瘤复发,并最终改善患者预后。