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Abstract：
The substantial heterogeneity exhibited by head and neck cancer (HNC), encompassing diverse cellular origins, anatomical locations, and etiological contributors, combined with the prevalent late-stage diagnosis, poses significant challenges for clinical management. Genomic sequencing endeavors have revealed extensive alterations in key signaling pathways that regulate cellular proliferation and survival. Initiatives to engineer therapies targeting these dysregulated pathways are underway, with several candidate molecules progressing to clinical evaluation phases, including FDA approval for agents like the EGFR-targeting monoclonal antibody cetuximab for K-RAS wild-type, EGFR-mutant HNSCC treatment. Non-coding RNAs (ncRNAs), owing to their enhanced stability in biological fluids and their important roles in intracellular and intercellular signaling within HNC contexts, are now recognized as potent biomarkers for disease management, catalyzing further refined diagnostic and therapeutic strategies, edging closer to the personalized medicine desideratum. Enhanced comprehension of the genomic and immunological landscapes characteristic of HNC is anticipated to facilitate a more rigorous assessment of targeted therapies benefits and limitations, optimize their clinical deployment, and foster innovative advancements in treatment approaches. This review presents an update on the molecular mechanisms and mutational spectrum of HNC driving the oncogenesis of head and neck malignancies and explores their implications for advancing diagnostic methodologies and precision therapeutics.
摘要：
头颈癌（HNC）表现出的实质性异质性，包括不同的细胞起源，解剖位置,和病因贡献者，结合普遍的晚期诊断，对临床管理提出了重大挑战。基因组测序努力已经揭示了调节细胞增殖和存活的关键信号传导途径的广泛改变。针对这些失调途径的工程疗法的计划正在进行中，随着几种候选分子进入临床评估阶段，包括FDA批准针对K-RAS野生型的EGFR靶向单克隆抗体西妥昔单抗等药物，EGFR-突变型HNSCC治疗。非编码RNA（ncRNAs），由于它们在生物体液中的稳定性增强，以及它们在HNC环境中的细胞内和细胞间信号传导中的重要作用，现在被认为是疾病管理的有效生物标志物，催化进一步完善的诊断和治疗策略，越来越接近个性化医疗的需求。增强对HNC基因组和免疫景观特征的理解，预计将有助于对靶向治疗的益处和局限性进行更严格的评估。优化他们的临床部署，并促进治疗方法的创新进步。这篇综述介绍了HNC驱动头颈部恶性肿瘤发生的分子机制和突变谱的最新研究，并探讨了它们对推进诊断方法和精准治疗的意义。
