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 xerostomia, 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.

中文翻译：

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辐射诱导的唾液腺功能障碍的慢性表型


头颈癌 （HNC） 是第六大确诊癌症，治疗通常包括手术切除肿瘤，然后进行电离辐射 （IR）。虽然 IR 在控制肿瘤生长方面表现出色，但由于唾液腺靠近常见的肿瘤部位，因此通常会损害唾液腺。唾液腺的辐射损伤导致分泌功能丧失，导致唾液流量严重和慢性减少。这导致患者报告的口干感，称为口干症，这显着降低了 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。现有的疗法可以暂时缓解症状，但没有永久恢复功能的护理标准。在理解对放疗的慢性机制反应以及停止治疗后数月至数年内可以给予的治疗方面存在很大差距。HNC 病例正在稳步上升;特别是，被诊断患有非致命性人瘤病毒 + HNC 的年轻患者人数持续增加。HNC 诊断数量的增加和预后的改善导致更多的口干患者患有口干症，这凸显了对恢复性治疗的需求日益增长。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、纤维化和神经元反应失调。目前，有前景的治疗方案包括腺病毒基因转移和干细胞疗法。 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。了解对辐射的慢性反应为开发逆转唾液腺损伤和改善 HNC 幸存者生活质量的新疗法提供了潜力。