Department of Nutritional Sciences, The University of Arizona, Tucson, AZ, USA.
J Dent Res. 2024 Jul;103(8):778-786. doi: 10.1177/00220345241252396. Epub 2024 May 29.
Head and neck cancer (HNC) is the sixth most diagnosed cancer, and treatment typically consists of surgical removal of the tumor followed by ionizing radiation (IR). While excellent at controlling tumor growth, IR often damages salivary glands due to their proximity to common tumor sites. Radiation damage to salivary glands results in loss of secretory function, causing severe and chronic reductions in salivary flow. This leads to the patient-reported sensation of dry mouth, termed , which significantly reduces quality of life for HNC patients and survivors. The mechanisms underlying salivary gland damage remain elusive, and therefore, treatment options are scarce. Available therapies provide temporary symptom relief, but there is no standard of care for permanent restoration of function. There is a significant gap in understanding the chronic mechanistic responses to radiation as well as treatments that can be given in the months to years following cessation of treatment. HNC cases are steadily rising; particularly, the number of young patients diagnosed with nonfatal human papillomavirus + HNC continues to increase. The growing number of HNC diagnoses and improved prognoses results in more people living with xerostomia, which highlights the mounting need for restorative treatments. Mechanisms underlying chronic damage include decreases in acinar differentiation markers, increases in acinar cell proliferation, immune and inflammatory dysregulation, and metabolic changes including increases in amino acids and reductions in glycolysis and oxidative phosphorylation, fibrosis, and dysregulated neuronal responses. Currently, promising treatment options include adenoviral gene transfers and stem cell therapy. Thus, this review describes in depth known mechanisms contributing to chronic damage and discusses therapeutic advances in treating chronically damaged glands. Understanding the chronic response to radiation offers potential in development of new therapeutics to reverse salivary gland damage and improve the quality of life of HNC survivors.
头颈部癌症（HNC）是第六大常见癌症，其治疗方法通常包括手术切除肿瘤，然后进行电离辐射（IR）。虽然 IR 非常擅长控制肿瘤生长，但由于其靠近常见肿瘤部位，IR 经常会损伤唾液腺。辐射对唾液腺的损伤会导致分泌功能丧失，导致唾液流量严重且慢性减少。这会导致患者出现口干的感觉，即 ，这会显著降低 HNC 患者和幸存者的生活质量。唾液腺损伤的机制仍然难以捉摸，因此治疗选择很少。现有的治疗方法只能提供暂时的症状缓解，但对于永久性恢复功能没有标准的治疗方法。人们对停止治疗后数月至数年期间辐射的慢性机制反应以及可以进行的治疗方法的理解存在很大差距。HNC 病例稳步上升；特别是，诊断出患有非致命性人类乳头瘤病毒+ HNC 的年轻患者数量继续增加。HNC 诊断数量的增加和预后的改善导致更多的人患有口干症，这凸显了对恢复性治疗的需求不断增加。慢性损伤的机制包括腺泡分化标志物减少、腺泡细胞增殖增加、免疫和炎症失调以及代谢变化（包括氨基酸增加和糖酵解和氧化磷酸化减少、纤维化和失调的神经元反应）。目前，有前途的治疗选择包括腺病毒基因转移和干细胞治疗。因此，本综述深入描述了导致慢性损伤的已知机制，并讨论了治疗慢性损伤腺体的治疗进展。了解辐射的慢性反应为开发新的治疗方法以逆转唾液腺损伤和提高 HNC 幸存者的生活质量提供了潜力。
