Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions
Abstract
:1. Introduction
2. Clinical Presentation
3. Animal Models Provide Mechanistic Insight into Radiation-Induced Salivary Gland Dysfunction
3.1. DNA Damage, Insufficient DNA Repair and Cell Cycle Arrest
3.2. Reactive Oxygen Species Generation
3.3. Dysregulated Calcium Signaling
3.4. Generation of Inflammatory Responses
3.5. Apoptosis, Autophagy and Cellular Senescence
3.6. Neuronal and Vascular Changes
3.7. Stem/Progenitor Cell Dysfunction
3.8. Compensatory Proliferation
3.9. Alterations in Cell Structure
3.10. Fibrosis
3.11. Immunomodulation
4. Bystander Effect: Potential Role for Purinergic Signaling
4.1. ATP Release
4.2. Dysregulated Calcium Signaling
4.3. MAPK Signaling
4.4. COX-2/Prostaglandin E2 Signaling
4.5. DNA Damage Response
4.6. Reactive Oxygen Species and TGF-β1
4.7. Immunomodulation
5. Therapeutics
5.1. Salivary Gland-Sparing Techniques
5.1.1. Dosing Strategies
5.1.2. Intensity Modulated Radiation Therapy (IMRT)
5.1.3. Volumetric Modulated Arc Therapy (VMAT)
5.1.4. Proton Beam Radiotherapy (PBRT)
5.1.5. Intraoral Stents and Temporary Submandibular Gland (SMG) Transplantation
5.2. Symptom Relief
5.2.1. Artificial Saliva
5.2.2. Sialagogues
5.3. Radioprotection
5.3.1. Amifostine
5.3.2. Promising Preclinical Studies
5.4. Regeneration
5.4.1. Gene Therapy
5.4.2. Stem Cell Therapies
5.4.3. Pharmacological Approaches
6. Summary
Author Contributions
Funding
Conflicts of Interest
References
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Jasmer, K.J.; Gilman, K.E.; Muñoz Forti, K.; Weisman, G.A.; Limesand, K.H. Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions. J. Clin. Med. 2020, 9, 4095. https://doi.org/10.3390/jcm9124095
Jasmer KJ, Gilman KE, Muñoz Forti K, Weisman GA, Limesand KH. Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions. Journal of Clinical Medicine. 2020; 9(12):4095. https://doi.org/10.3390/jcm9124095
Chicago/Turabian StyleJasmer, Kimberly J., Kristy E. Gilman, Kevin Muñoz Forti, Gary A. Weisman, and Kirsten H. Limesand. 2020. "Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions" Journal of Clinical Medicine 9, no. 12: 4095. https://doi.org/10.3390/jcm9124095
APA StyleJasmer, K. J., Gilman, K. E., Muñoz Forti, K., Weisman, G. A., & Limesand, K. H. (2020). Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions. Journal of Clinical Medicine, 9(12), 4095. https://doi.org/10.3390/jcm9124095