RAS基因在癌症中的异常调控已经有几十年的研究，大量努力已经致力于开发能够降低RAS表达或阻断RAS活化的药物。近期RAS抑制剂在癌症患者中的引入凸显了对于了解头颈部癌（HNC）中RAS变异的重要性。在这方面，我们检查了有关HNC中RAS变异和通路激活的已发表研究结果，并总结了它们在HNC的起始、进展和转移中的作用。具体而言，我们关注了突变RAS在肿瘤细胞信号传导中的内在作用以及其在决定肿瘤微环境（TME）异质性中的外在作用，包括促进血管生成和增强免疫逃逸。最后，我们总结了RAS变异在抗癌治疗中的内在和外在作用，勾勒出使用单一药物或与其他治疗药物联合治疗以靶向RAS的潜力，以应对具有RAS激活肿瘤的HNC患者。版权所有© 2023. 由Elsevier B.V.出版。

RAS genes are known to be dysregulated in cancer for several decades, and substantial effort has been dedicated to develop agents that reduce RAS expression or block RAS activation. The recent introduction of RAS inhibitors for cancer patients highlights the importance of comprehending RAS alterations in head and neck cancer (HNC). In this regard, we examine the published findings on RAS alterations and pathway activations in HNC, and summarize their role in HNC initiation, progression, and metastasis. Specifically, we focus on the intrinsic role of mutated-RAS on tumor cell signaling and its extrinsic role in determining tumor-microenvironment (TME) heterogeneity, including promoting angiogenesis and enhancing immune escape. Lastly, we summarize the intrinsic and extrinsic role of RAS alterations on therapy resistance to outline the potential of targeting RAS using a single agent or in combination with other therapeutic agents for HNC patients with RAS-activated tumors.Copyright © 2023. Published by Elsevier B.V.