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CRISPR-Cas技术在头颈癌领域的变革:靶向治疗的新时代。

The CRISPR-Cas revolution in head and neck cancer: a new era of targeted therapy.

作者信息

Hashemi Mohsen, Khanaghah Xaniar Mohmmadi, Nahand Javid Sadri

机构信息

Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, 15731, Iran.

Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 15731, Iran.

出版信息

Funct Integr Genomics. 2025 May 30;25(1):113. doi: 10.1007/s10142-025-01612-2.

DOI:10.1007/s10142-025-01612-2
PMID:40445465
Abstract

Head and neck cancer (HNC) encompasses a diverse array of malignancies impacting the anatomical structures of the head and neck region, ranking as the seventh most prevalent cancer type globally. The occurrence and advancement of HNC are intricately linked to mutations and disruptions within critical signaling pathways, accentuating the imperative for targeted therapeutic interventions to rectify these genetic aberrations. Traditional treatment modalities, including surgical intervention and adjuvant chemotherapy or radiotherapy, frequently culminate in considerable morbidity and suboptimal prognoses. Recently, the CRISPR-Cas system has emerged as a revolutionary gene-editing platform, poised to redefine therapeutic approaches in gene therapy and oncological research. Despite its potential, CRISPR-Cas faces challenges such as off-target effects, delivery inefficiencies, and immunogenicity, which must be addressed for clinical success. This review meticulously evaluates the progress in CRISPR-Cas technologies aimed at targeting essential signaling pathways implicated in HNC, addressing current challenges while highlighting optimal targets, Cas nucleases, and innovative delivery mechanisms, thereby elucidating the therapeutic potential and clinical applicability of the CRISPR-Cas paradigm in the management of HNC.

摘要

头颈癌(HNC)涵盖了一系列影响头颈部区域解剖结构的恶性肿瘤,是全球第七大常见癌症类型。HNC的发生和发展与关键信号通路中的突变和破坏密切相关,这凸显了进行靶向治疗干预以纠正这些基因异常的紧迫性。传统的治疗方式,包括手术干预以及辅助化疗或放疗,常常导致相当高的发病率和不理想的预后。最近,CRISPR-Cas系统已成为一个革命性的基因编辑平台,有望重新定义基因治疗和肿瘤学研究中的治疗方法。尽管具有潜力,但CRISPR-Cas面临着诸如脱靶效应、递送效率低下和免疫原性等挑战,要想在临床上取得成功,必须解决这些问题。本综述精心评估了旨在靶向HNC中关键信号通路的CRISPR-Cas技术的进展,在解决当前挑战的同时突出了最佳靶点、Cas核酸酶和创新递送机制,从而阐明了CRISPR-Cas模式在HNC管理中的治疗潜力和临床适用性。

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本文引用的文献

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Tobacco and alcohol use are the risk factors responsible for the greatest burden of head and neck cancers: a study from the Global Burden of Disease Study 2019.烟草和酒精使用是导致头颈癌负担最重的风险因素:一项来自《2019年全球疾病负担研究》的研究。
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Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCC.基于CRISPR-Cas9筛选解析增殖必需基因特征以预测头颈部鳞状细胞癌的预后并表征其免疫微环境。
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Mannose and PMI depletion overcomes radiation resistance in HPV-negative head and neck cancer.
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SMYD3 drives cell cycle and epithelial-mesenchymal transition pathways through dual gene transcriptional repression and activation in HPV-negative head and neck cancer.SMYD3通过对人乳头瘤病毒阴性头颈癌中的双基因进行转录抑制和激活来驱动细胞周期和上皮-间质转化途径。
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Gene-Silencing Therapeutic Approaches Targeting PI3K/Akt/mTOR Signaling in Degenerative Intervertebral Disk Cells: An In Vitro Comparative Study Between RNA Interference and CRISPR-Cas9.针对退变椎间盘细胞中PI3K/Akt/mTOR信号通路的基因沉默治疗方法:RNA干扰与CRISPR-Cas9的体外比较研究
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The critical role of Gαi3 in oral squamous cell carcinoma cell growth.Gαi3在口腔鳞状细胞癌细胞生长中的关键作用。
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NF-κB-activated oncogene inhibition strategy for cancer gene therapy.NF-κB 激活的致癌基因抑制策略在癌症基因治疗中的应用。
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Let's make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment.让我们个体化治疗:CRISPR 工具在操控细胞死亡通路以治疗癌症中的应用。
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