Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions

Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions
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DOI:
10.3390/jcm9124095
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发表时间:
2020-12-18
影响因子:
3.9
通讯作者:
Limesand KH
Limesand KH
中科院分区:
医学2区
文献类型:
--
作者:
Jasmer KJ;Gilman KE;Muñoz Forti K;Weisman GA;Limesand KH

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治疗头颈部癌症的放射治疗 (RT) 后,唾液腺会遭受附带损伤,导致并发症,包括粘膜炎、口干症和唾液分泌不足。尽管保留唾液腺技术和改进的给药策略,长期功能减退仍然是一个重大问题。目前的治疗干预措施可以暂时缓解症状,但不能解决不可逆的腺体损伤。在这篇综述中,我们总结了目前对放疗引起的唾液分泌不足机制的理解,并为未来的机制研究提供了框架。在已发表的研究放疗引起的唾液腺功能障碍机制的研究中,一个明显的差距涉及辐射通过旁分泌、自分泌和直接细胞间相互作用对邻近未受辐射组织的影响,这在其他放疗引起的损伤模型中创造了旁观者效应。我们假设涉及 P2 核苷酸受体的嘌呤能受体信号传导可能在介导旁观者效应中发挥关键作用。我们还讨论了有前景的新治疗方法,以预防放疗引起的唾液腺损伤。
Salivary glands sustain collateral damage following radiotherapy (RT) to treat cancers of the head and neck, leading to complications, including mucositis, xerostomia and hyposalivation. Despite salivary gland-sparing techniques and modified dosing strategies, long-term hypofunction remains a significant problem. Current therapeutic interventions provide temporary symptom relief, but do not address irreversible glandular damage. In this review, we summarize the current understanding of mechanisms involved in RT-induced hyposalivation and provide a framework for future mechanistic studies. One glaring gap in published studies investigating RT-induced mechanisms of salivary gland dysfunction concerns the effect of irradiation on adjacent non-irradiated tissue via paracrine, autocrine and direct cell–cell interactions, coined the bystander effect in other models of RT-induced damage. We hypothesize that purinergic receptor signaling involving P2 nucleotide receptors may play a key role in mediating the bystander effect. We also discuss promising new therapeutic approaches to prevent salivary gland damage due to RT.
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