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探索微小RNA疗法和肠道微生物群增强的嵌合抗原受体T细胞:推进胶质母细胞瘤干细胞靶向治疗的前沿进展。

Exploring miRNA therapies and gut microbiome-enhanced CAR-T cells: advancing frontiers in glioblastoma stem cell targeting.

作者信息

Sandhanam K, Tamilanban T, Bhattacharjee Bedanta, Manasa K

机构信息

Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Chengalpattu, 603203, Tamil Nadu, India.

Department of Pharmacology, Girijananda Chowdhury University-Tezpur Campus, 784501, Assam, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar;398(3):2169-2207. doi: 10.1007/s00210-024-03479-9. Epub 2024 Oct 9.

Abstract

Glioblastoma multiforme (GBM) presents a formidable challenge in oncology due to its aggressive nature and resistance to conventional treatments. Recent advancements propose a novel therapeutic strategy combining microRNA-based therapies, chimeric antigen receptor-T (CAR-T) cells, and gut microbiome modulation to target GBM stem cells and transform cancer treatment. MicroRNA therapies show promise in regulating key signalling pathways implicated in GBM progression, offering the potential to disrupt GBM stem cell renewal. CAR-T cell therapy, initially successful in blood cancers, is being adapted to target GBM by genetically engineering T cells to recognise and eliminate GBM stem cell-specific antigens. Despite early successes, challenges like the immunosuppressive tumour microenvironment persist. Additionally, recent research has uncovered a link between the gut microbiome and GBM, suggesting that gut dysbiosis can influence systemic inflammation and immune responses. Novel strategies to modulate the gut microbiome are emerging, enhancing the efficacy of microRNA therapies and CAR-T cell treatments. This combined approach highlights the synergistic potential of these innovative therapies in GBM treatment, aiming to eradicate primary tumours and prevent recurrence, thereby improving patient prognosis and quality of life. Ongoing research and clinical trials are crucial to fully exploit this promising frontier in GBM therapy, offering hope to patients grappling with this devastating disease.

摘要

多形性胶质母细胞瘤(GBM)因其侵袭性和对传统治疗的耐药性,在肿瘤学领域构成了巨大挑战。最近的进展提出了一种新的治疗策略,将基于微小RNA的疗法、嵌合抗原受体T细胞(CAR-T)和肠道微生物群调节相结合,以靶向GBM干细胞并变革癌症治疗。微小RNA疗法在调节与GBM进展相关的关键信号通路方面显示出前景,有可能破坏GBM干细胞的更新。CAR-T细胞疗法最初在血液癌症中取得成功,目前正通过基因工程改造T细胞以识别和消除GBM干细胞特异性抗原,从而使其适用于GBM治疗。尽管取得了早期成功,但诸如免疫抑制性肿瘤微环境等挑战依然存在。此外,最近的研究发现了肠道微生物群与GBM之间的联系,表明肠道生态失调会影响全身炎症和免疫反应。调节肠道微生物群的新策略正在出现,可提高微小RNA疗法和CAR-T细胞治疗的疗效。这种联合方法突出了这些创新疗法在GBM治疗中的协同潜力,旨在根除原发性肿瘤并预防复发,从而改善患者的预后和生活质量。正在进行的研究和临床试验对于充分利用GBM治疗这一充满希望的前沿领域至关重要,为与这种毁灭性疾病作斗争的患者带来了希望。

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