Oral and oropharyngeal squamous cell carcinomas (OSCC and OPSCC), two major sub-types of Head and Neck cancer, remain associated with significant morbidity and exhibit poor prognosis, with limited response to conventional therapies in advanced stages. Recent therapeutic strategies have increasingly focused on molecular targets involved in tumor proliferation, angiogenesis, and immune evasion. This overview provides a concise synthesis of targeted therapies under investigation or already in clinical use, including monoclonal antibodies against epidermal growth factor receptor (EGFR) (e.g., cetuximab) and immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab), as well as inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) or agents targeting angiogenic and intracellular signaling pathways such as VEGF and mTOR. Alongside these novel agents, growing interest surrounds the repurposing of established pharmacological agents which appear to modulate tumor-related inflammation, metabolic dysregulation, and epithelial-to-mesenchymal transition. Metformin and statins, for instance, have demonstrated anti-proliferative and pro-apoptotic effects in preclinical OSCC models. Notably, recent evidence suggests that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, may improve survival specifically in patients with PIK3CA-altered Head and Neck tumors, potentially through modulation of the COX-2/PGE2 axis. Although prospective evidence remains limited and somewhat heterogeneous, existing preclinical and observational studies suggest that these agents may improve survival and reduce treatment-related toxicity, further pointing to the relevance of molecular stratification in guiding future repurposing strategies. This article aims to map the current therapeutic landscape, highlighting both established molecular targets and emerging repositioned drugs in the management of OSCC and OPSCC.
口腔鳞状细胞癌（OSCC）与口咽鳞状细胞癌（OPSCC）作为头颈癌的两大主要亚型，仍具有较高的致残率且预后较差，晚期患者对常规治疗的反应有限。近年来，治疗策略日益聚焦于肿瘤增殖、血管生成及免疫逃逸相关的分子靶点。本文综述了当前处于研究阶段或已投入临床应用的靶向治疗策略，包括针对表皮生长因子受体（EGFR）的单克隆抗体（如西妥昔单抗）、免疫检查点抑制剂（如纳武利尤单抗、帕博利珠单抗），以及程序性死亡蛋白1（PD-1）及其配体（PD-L1）抑制剂，或靶向血管内皮生长因子（VEGF）、哺乳动物雷帕霉素靶蛋白（mTOR）等血管生成及细胞内信号通路的药物。与此同时，对现有药物的再利用研究日益受到关注，这些药物显示出调节肿瘤相关炎症、代谢紊乱及上皮-间质转化的潜力。例如二甲双胍和他汀类药物在临床前OSCC模型中已证实具有抗增殖和促凋亡作用。值得注意的是，最新证据表明，包括阿司匹林在内的非甾体抗炎药（NSAIDs）规律使用可能通过调节COX-2/PGE2轴，特异性地改善PIK3CA基因突变的头颈癌患者生存。尽管前瞻性证据仍有限且存在异质性，现有临床前及观察性研究表明这些药物可能提升生存率并降低治疗相关毒性，进一步提示分子分型对指导未来药物再利用策略的重要性。本文旨在梳理当前治疗格局，重点阐述OSCC与OPSCC治疗中已确立的分子靶点及新兴的再定位药物。
Targeted Therapies in Oral and Oropharyngeal Cancer: An Overview of Emerging and Repurposed Agents
肿瘤(癌症)患者之家