Elhami Anis, Ghasemzadeh Shabnam, Emrahoglu Sahand, Ghasemzadeh Nasim, Mivehchi Hassan, Beykoylu Mehmet, Ashrafpour Mahshad, Ayoubi Saminalsadat, Tabari Mohammad Amin Khazeei
Faculty of Dentistry, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Faculty of Dentistry, Qazvin University of Medical Sciences, Qazvin, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 14. doi: 10.1007/s00210-025-04142-7.
Malignancies of the oral cavity, oropharynx, hypopharynx, and larynx rank as the seventh most prevalent cancers globally, characterized by high morbidity and mortality. Despite advancements in conventional therapies, these cancers often demonstrate recurrence and treatment resistance. This review investigates ferroptosis, an iron-dependent regulated cell death mechanism, as a novel therapeutic target to overcome resistance and recurrence in these cancers. A narrative review study was conducted using online databases, including PubMed, Google Scholar, Scopus, and Web of Science. The search incorporated keywords such as "ferroptosis", "oral squamous cell carcinoma", "oropharyngeal cancer", "hypopharyngeal cancer", "laryngeal cancer", "iron metabolism", and "lipid peroxidation". Studies focusing on molecular mechanisms, ferroptosis regulation, and therapeutic applications were included. Key findings highlighted the involvement of genes like CA9, CAV1, and SLC7 A11 in oral squamous cell carcinoma (OSCC), contributing to progression and resistance. Ferroptosis inducers such as resveratrol and quercetin effectively promoted ferroptosis in OSCC by targeting pathways like p53/SLC7 A11. In hypopharyngeal and oropharyngeal cancers, agents like ascorbic acid and RSL3 enhanced lipid peroxidation, while laryngeal cancers showed resistance through molecules like SLC3 A2 and KPNA2, which could be counteracted with targeted therapies. Nanotechnology-based approaches, including photodynamic therapy and nanofiber membranes, offer potential for localized and effective ferroptosis induction. Ferroptosis holds promise as a therapeutic strategy for treating head and neck cancers by addressing treatment resistance and recurrence. Future research should focus on optimizing combination therapies, understanding molecular heterogeneity, and translating preclinical findings into clinical applications to improve patient outcomes.
口腔、口咽、下咽和喉的恶性肿瘤是全球第七大常见癌症，其发病率和死亡率都很高。尽管传统疗法取得了进展，但这些癌症往往会复发且具有治疗抗性。本综述研究了铁死亡（一种铁依赖性调节性细胞死亡机制），将其作为克服这些癌症抗性和复发的新型治疗靶点。我们使用在线数据库（包括PubMed、谷歌学术、Scopus和科学网）进行了一项叙述性综述研究。搜索关键词包括“铁死亡”“口腔鳞状细胞癌”“口咽癌”“下咽癌”“喉癌”“铁代谢”和“脂质过氧化”。纳入了关注分子机制、铁死亡调节和治疗应用的研究。主要研究结果强调了CA9、CAV1和SLC7A11等基因在口腔鳞状细胞癌（OSCC）中的作用，这些基因促进了肿瘤进展和抗性。白藜芦醇和槲皮素等铁死亡诱导剂通过靶向p53/SLC7A11等途径有效地促进了OSCC中的铁死亡。在下咽癌和口咽癌中，抗坏血酸和RSL3等药物增强了脂质过氧化，而喉癌则通过SLC3A2和KPNA2等分子表现出抗性，针对这些分子的靶向治疗可以抵消这种抗性。基于纳米技术的方法，包括光动力疗法和纳米纤维膜，为局部有效诱导铁死亡提供了潜力。铁死亡有望成为一种治疗策略，通过解决治疗抗性和复发问题来治疗头颈癌。未来的研究应集中在优化联合治疗、理解分子异质性以及将临床前研究结果转化为临床应用，以改善患者预后。
