头颈癌中的驱动蛋白超家族蛋白：机制、临床意义和治疗潜力。

文献信息

中文摘要

头颈癌，尤其是头颈部鳞状细胞癌（HNSCC），仍然是癌症相关发病率和死亡率的重要原因。尽管手术、放疗、化疗、靶向治疗和免疫治疗改善了疾病管理，但晚期或复发疾病患者的预后仍然很差。越来越多的证据表明，驱动蛋白超家族蛋白（KIFs），即参与细胞内运输和染色体动力学的基于微管的分子马达，在头颈癌中具有重要作用。本综述审查了关于头颈癌中KIF失调的当前证据，特别强调它们对肿瘤生物学、调控机制、临床相关性和治疗潜力的贡献。本叙述性综述审查了关于KIF参与头颈癌主要特征的同行评审临床前和临床研究，包括细胞增殖、侵袭、转移、上皮-间质转化（EMT）、癌症干性、细胞周期进展、凋亡和治疗耐药。我们还考虑了关于调控机制的证据，包括非编码RNA、泛素介导的蛋白水解和N6-甲基腺苷（m6A）修饰，以及研究KIF作为预后生物标志物或治疗靶点的研究。现有证据支持几种KIF在头颈癌进展中的重要作用，特别是通过影响细胞周期调控、存活、迁移和致癌信号传导。然而，KIF活性并非一致地具有致癌性。各个家族成员的作用似乎取决于肿瘤亚型、解剖部位、分子背景和人乳头瘤病毒（HPV）状态。此外，实验研究占主导地位以及临床队列相对较小限制了当前临床证据的强度。未来的研究应使用HPV和亚型分层模型以及整合的转录组学、蛋白质组学和表观遗传学方法，阐明各个KIF的情境特异性功能。在临床相关模型和更大、独立的患者队列中进行验证，对于确立其生物标志物价值将很重要。选择性驱动蛋白抑制剂也值得进一步研究，以确定这些蛋白是否可以有效地用于头颈癌的治疗干预。

英文摘要

Head and neck cancer, particularly head and neck squamous cell carcinoma (HNSCC), remains a substantial cause of cancer-related morbidity and mortality. Although surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy have improved disease management, the prognosis of patients with advanced or recurrent disease remains poor. Increasing evidence suggests that kinesin superfamily proteins (KIFs), microtubule-based molecular motors involved in intracellular transport and chromosome dynamics, have important roles in head and neck cancer. This review examines the current evidence on KIF dysregulation in head and neck cancer, with particular emphasis on their contributions to tumor biology, regulatory mechanisms, clinical relevance, and therapeutic potential. This narrative review examined peer-reviewed preclinical and clinical studies on KIF involvement in major features of head and neck cancer, including cell proliferation, invasion, metastasis, epithelial-to-mesenchymal transition (EMT), cancer stemness, cell-cycle progression, apoptosis, and treatment resistance. We also considered evidence on regulatory mechanisms, including non-coding RNAs, ubiquitin-mediated proteolysis, and N6-methyladenosine (m6A) modification, along with studies investigating KIFs as prognostic biomarkers or therapeutic targets. The available evidence supports an important role for several KIFs in head and neck cancer progression, particularly through effects on cell-cycle regulation, survival, migration, and oncogenic signaling. Nevertheless, KIF activity is not uniformly oncogenic. The effects of individual family members appear to depend on tumor subtype, anatomical site, molecular context, and human papillomavirus (HPV) status. In addition, the predominance of experimental studies and relatively small clinical cohorts limits the strength of current clinical evidence. Future studies should clarify the context-specific functions of individual KIFs using HPV- and subtype-stratified models and integrated transcriptomic, proteomic, and epigenetic approaches. Validation in clinically relevant models and larger, independent patient cohorts will be important for establishing their biomarker value. Selective kinesin inhibitors also warrant further investigation to determine whether these proteins can be effectively exploited for therapeutic intervention in head and neck cancer.