Cancer stem cell mechanisms and targeted therapeutic strategies in head and neck squamous cell carcinoma

IF 10.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-09-02 DOI:10.1016/j.canlet.2025.218015

Nagarajan Maharajan , Daniel S. Benyamien-Roufaeil , Robert A. Brown , Benjamin A. Portney , Aditi Banerjee , Michal Zalzman

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引用次数: 0

Abstract

Head and neck squamous cell carcinoma (HNSCC) originates in the epithelial lining of the oral cavity, pharynx, and larynx, with over 830,000 new cases diagnosed globally in 2020, making it the seventh most prevalent cancer. Despite treatment advances, high-grade HNSCCs remain associated with poor outcomes and a high risk of recurrence.

Although Cancer Stem Cells (CSCs) are rare in HNSCC tumors, they are key drivers of tumor relapses, as they evade apoptosis and survive current therapies through enhanced DNA repair and quiescence. This review integrates recent discoveries into a unified framework for understanding CSC mechanisms. It examines the role of pluripotency factors, biomarkers, replicative immortalization, metabolic reprogramming, redox regulation, and immune evasion in shaping CSC behavior and survival under treatment stress. Non-coding RNAs are also discussed as modulators of gene expression via epigenetic regulation in CSCs. Importantly, it highlights how these adaptive mechanisms intersect as potential vulnerabilities that could be exploited to eliminate CSCs through targeting multiple pathways.

Finally, it provides recent and emerging precision therapeutics, including CAR-T cells, immune checkpoint inhibitors, metabolic and redox-targeting agents, and epigenetic modulators currently in preclinical and clinical trials applications designed to eliminate CSCs and improve patient outcomes in HNSCC.

查看原文本刊更多论文

头颈部鳞状细胞癌的肿瘤干细胞机制和靶向治疗策略。

头颈部鳞状细胞癌（HNSCC）起源于口腔、咽和喉的上皮层，2020年全球新诊断病例超过83万例，成为第七大常见癌症。尽管治疗取得了进展，但高级别HNSCCs仍然与不良预后和高复发风险相关。尽管癌症干细胞（CSCs）在HNSCC肿瘤中很少见，但它们是肿瘤复发的关键驱动因素，因为它们逃避细胞凋亡，并通过增强DNA修复和静止在当前治疗中存活下来。这篇综述将最近的发现整合到一个理解CSC机制的统一框架中。它研究了多能性因子、生物标志物、复制永生、代谢重编程、氧化还原调节和免疫逃避在塑造CSC行为和治疗应激下的生存中的作用。非编码rna也被讨论作为基因表达调节剂通过表观遗传调控在CSCs。重要的是，它强调了这些自适应机制如何交叉作为潜在的漏洞，可以利用这些漏洞通过靶向多种途径来消除csc。最后，它提供了最新和新兴的精确治疗方法，包括CAR-T细胞，免疫检查点抑制剂，代谢和氧化还原靶向剂，以及表观遗传调节剂，目前在临床前和临床试验中应用，旨在消除CSCs并改善HNSCC患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.