Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006 Jiangxi, China.
Oxid Med Cell Longev. 2020 Jul 22;2020:5047987. doi: 10.1155/2020/5047987. eCollection 2020.
Head and neck cancer is a highly genetic and metabolic heterogeneous collection of malignancies of the lip, oral cavity, salivary glands, pharynx, esophagus, paranasal sinuses, and larynx with five-year survival rates ranging from 12% to 93%. Patients with head and neck cancer typically present with advanced stage III, IVa, or IVb disease and are treated with comprehensive modality including chemotherapy, radiotherapy, and surgery. Despite advancements in treatment modality and technique, noisome recurrence, invasiveness, and resistance as well as posttreatment complications severely influence survival rate and quality of life. Thus, new therapeutic strategies are urgently needed that offer enhanced efficacy with less toxicity. ROS in cancer cells plays a vital role in regulating cell death, DNA repair, stemness maintenance, metabolic reprogramming, and tumor microenvironment, all of which have been implicated in resistance to chemo-/radiotherapy of head and neck cancer. Adjusting ROS generation and elimination to reverse the resistance of cancer cells without impairing normal cells show great hope in improving the therapeutic efficacy of chemo-/radiotherapy of head and neck cancer. In the current review, we discuss the pivotal and targetable redox-regulating system including superoxide dismutases (SODs), tripeptide glutathione (GSH), thioredoxin (Trxs), peroxiredoxins (PRXs), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1), and mitochondria electron transporter chain (ETC) complexes and their roles in regulating ROS levels and their clinical significance implicated in chemo-/radiotherapy of head and neck cancer. We also summarize several old drugs (referred to as the non-anti-cancer drugs used in other diseases for a long time) and small molecular compounds as well as natural herbs which effectively modulate cellular ROS of head and neck cancer to synergize the efficacy of conventional chemo-/radiotherapy. Emerging interdisciplinary techniques including photodynamic, nanoparticle system, and Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy are promising measures to broaden the potency of ROS modulation for the benefit of chemo-/radiotherapy in head and neck cancer.
头颈部癌症是一组高度遗传和代谢异质性的恶性肿瘤，包括唇、口腔、唾液腺、咽、食管、副鼻窦和喉，五年生存率从 12%到 93%不等。头颈部癌症患者通常表现为晚期 III、IVa 或 IVb 期疾病，并采用包括化疗、放疗和手术在内的综合治疗方法进行治疗。尽管在治疗方式和技术方面取得了进展，但复发、侵袭性和耐药性以及治疗后并发症严重影响了生存率和生活质量。因此，迫切需要新的治疗策略，以提高疗效，降低毒性。癌细胞中的 ROS 在调节细胞死亡、DNA 修复、干细胞维持、代谢重编程和肿瘤微环境方面发挥着重要作用，这些都与头颈部癌症的化疗/放疗耐药性有关。调节 ROS 的产生和消除以逆转癌细胞的耐药性而不损害正常细胞，在提高头颈部癌症的化疗/放疗疗效方面显示出巨大的希望。在本综述中，我们讨论了关键的和可靶向的氧化还原调节系统，包括超氧化物歧化酶（SODs）、三肽谷胱甘肽（GSH）、硫氧还蛋白（Trxs）、过氧化物酶（PRXs）、核因子红细胞 2 相关因子 2/ Kelch 样 ECH 相关蛋白 1（Nrf2/keap1）和线粒体电子转运链（ETC）复合物，以及它们在调节 ROS 水平及其在头颈部癌症化疗/放疗中的临床意义方面的作用。我们还总结了几种老药（长期用于其他疾病的非抗癌药物）和小分子化合物以及天然草药，它们能有效调节头颈部癌细胞的细胞 ROS，以协同常规化疗/放疗的疗效。新兴的跨学科技术，包括光动力、纳米粒子系统和 Bio-Electro-Magnetic-Energy-Regulation（BEMER）治疗，是扩大 ROS 调节作用的有前途的措施，有利于头颈部癌症的化疗/放疗。
