头颈癌 (HNC) 表现出巨大的异质性，包括不同的细胞起源、解剖位置和病因学因素，加上普遍的晚期诊断，给临床治疗带来了重大挑战。基因组测序工作揭示了调节细胞增殖和存活的关键信号通路的广泛改变。针对这些失调途径的工程治疗方案正在进行中，多个候选分子已进入临床评估阶段，包括 FDA 批准用于 K-RAS 野生型、EGFR 突变型 HNSCC 治疗的 EGFR 靶向单克隆抗体西妥昔单抗等药物。非编码 RNA (ncRNA) 由于其在生物体液中增强的稳定性及其在 HNC 背景下细胞内和细胞间信号转导中的重要作用，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，更接近于个性化医疗的迫切需要。增强对 HNC 基因组和免疫学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，优化其临床部署，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情况，并探讨了它们对先进诊断方法和精准治疗的影响。版权所有 © 2024 Constantin, Chifiriuc, Bleotu, Vrancianu, Cristian, Bertesteanu, Grigore和贝尔泰斯泰亚努。

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.Copyright © 2024 Constantin, Chifiriuc, Bleotu, Vrancianu, Cristian, Bertesteanu, Grigore and Bertesteanu.