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揭示癌症干细胞治疗的未来:新兴创新的叙事探索

英文原题:Unveiling the future of cancer stem cell therapy: a narrative exploration of emerging innovations.

PubMed 2025/03/22(内容时间) Discov Oncol Q3 · IF 2.8(JCR 2025)

研究概要

肿瘤干细胞(CSC)是肿瘤内的关键亚群,其定义为具有自我更新、分化和肿瘤起始能力。

中文摘要

癌症干细胞(CSC)是肿瘤中的关键亚群,以自我更新、分化和启动肿瘤的能力为特征。这些独特特性会促进肿瘤进展、转移,并对化疗和放疗等常规治疗产生耐药,常导致癌症复发和患者结局不佳。因此,CSC 已成为开发先进癌症疗法的重点。本综述介绍 CSC 靶向治疗的进展,包括CAR-T(CAR-T)细胞疗法、免疫治疗、分子靶向及基于纳米颗粒的药物递送系统。综述探讨植物来源化合物和基因编辑技术(如成簇规律间隔短回文重复序列 CRISPR)提高精准性、减少副作用的潜力。研究考察了对 CSC 存活至关重要的代谢通路作为治疗靶点,包括线粒体动态、线粒体自噬(由 dynamin 相关蛋白 1[DRP1]和 PINK1/Parkin 通路调控)、一碳代谢、氨基酸代谢[涉及谷氨酰胺酶(GLS)和谷氨酸脱氢酶(GDH)等酶]、脂质代谢,以及由缺氧诱导因子(HIF-1 和 HIF-2)介导的缺氧性代谢重编程。本文还讨论 CSC 通过自噬、代谢灵活性,以及由 α-酮戊二酸、琥珀酸和富马酸等代谢物介导的表观遗传调控实现适应的能力。此外,细胞外囊泡和烟酰胺腺嘌呤二核苷酸(NAD)代谢被认为在氧化还原平衡、DNA 修复和表观遗传修饰中发挥关键作用。要应对肿瘤异质性、免疫逃逸和治疗持久性等挑战,需要跨学科协作。推进 CSC 靶向疗法对于克服耐药和预防癌症复发至关重要,并可为变革性癌症治疗铺路。本综述强调利用创新技术并促进合作,对革新癌症治疗的重要性。

展开英文摘要原文

Cancer stem cells (CSCs), are a critical subpopulation within tumours, and are defined by their capacity for self-renewal, differentiation, and tumour initiation. These unique traits contribute to tumour progression, metastasis, and resistance to conventional treatments like chemotherapy and radiotherapy, often resulting in cancer recurrence and poor patient outcomes. As such, CSCs have become focal points in developing advanced cancer therapies. This review highlights progress in CSC-targeted treatments, including chimeric antigen receptor T-cell (CAR-T) therapy, immunotherapy, molecular targeting, and nanoparticle-based drug delivery systems. Plant-derived compounds and gene-editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR), are explored for their potential to enhance precision and minimize side effects. Metabolic pathways integral to CSC survival, such as mitochondrial dynamics, mitophagy (regulated by dynamin-related protein 1 [DRP1] and the PINK1/Parkin pathway), one-carbon metabolism, amino acid metabolism (involving enzymes like glutaminase (GLS) and glutamate dehydrogenase (GDH]), lipid metabolism, and hypoxia-induced metabolic reprogramming mediated by hypoxia-inducible factors (HIF-1 and HIF-2 ), are examined as therapeutic targets. The adaptability of CSCs through autophagy, metabolic flexibility, and epigenetic regulation by metabolites like -ketoglutarate, succinate, and fumarate is discussed. Additionally, extracellular vesicles and nicotinamide adenine dinucleotide (NAD ) metabolism are identified as pivotal in redox balance, DNA repair, and epigenetic modifications. Addressing challenges such as tumour heterogeneity, immune evasion, and treatment durability requires interdisciplinary collaboration. Advancing CSC-targeted therapies is essential for overcoming drug resistance and preventing cancer relapse, paving the way for transformative cancer treatments. This review underscores the importance of leveraging innovative technologies and fostering collaboration to revolutionize cancer treatment.

论文信息

作者
Obisi JN、Abimbola ANJ、Babaleye OA、Atidoglo PK、Usin SG、Nwanaforo EO、Patrick-Inezi FS、Fasogbon IV
第一作者单位
Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
通讯作者单位
Department of Biochemistry/Research and Publications, Kampala International University, P.O. Box 20000, Kampala, Uganda. daniel.ejimuti@kiu.ac.ug.
文献类型
综述
期刊
Discover oncology2025 Mar 22
原文标识
PubMed 40120008 · DOI 10.1007/s12672-025-02102-4