Since its introduction, the use of cetuximab in the treatment of head and neck squamous cell carcinoma (HNSCC) has experienced an evolution. Currently, cetuximab associated with radiotherapy is limited to the treatment of patients affected by a locally advanced malignancy and unfit for cisplatin. However, reliable biomarkers of cetuximab efficacy in this cancer setting are still lacking. This review focuses on the mechanisms of action of cetuximab, highlighting, in particular, the consequences of the binding to EGFR, and the pathways involved in the development of adverse events or acquired resistance. Indeed, adverse events, such as skin rash, have been associated with cetuximab efficacy in HNSCC several times. Acquired resistance is associated with microenvironment plasticity, which is, in turn, characterized by an increased immune infiltrate. The better definition of patients eligible for this kind of therapy could improve HNSCC management, possibly proposing a combined treatment with radiotherapy, cetuximab and immune checkpoint inhibitors as recently investigated.

自推出以来，西妥昔单抗在头颈部鳞状细胞癌 (HNSCC) 治疗中的应用经历了一次演变。目前，与放疗相关的西妥昔单抗仅限于治疗受局部晚期恶性肿瘤影响且不适合顺铂的患者。然而，仍然缺乏西妥昔单抗在这种癌症环境中有效性的可靠生物标志物。本综述重点关注西妥昔单抗的作用机制，特别强调与 EGFR 结合的后果，以及与不良事件或获得性耐药发生相关的途径。事实上，皮疹等不良事件多次与西妥昔单抗在 HNSCC 中的疗效相关。获得性耐药与微环境可塑性有关，而微环境可塑性又以免疫浸润增加为特征。