Radiation-induced salivary gland dysfunction: Mechanisms, therapeutics and future directions

Kimberly J. Jasmer, Kristy E. Gilman, Kevin Muñoz Forti, Gary A. Weisman, Kirsten H. Limesand

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number4095
Pages (from-to)1-37
Number of pages37
JournalJournal of Clinical Medicine
Volume9
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • Bystander effect
  • Head and neck cancer
  • Hyposalivation
  • P2 receptors
  • Purinergic signaling
  • Radiation
  • Radioprotection
  • Saliva
  • Salivary gland
  • Xerostomia

ASJC Scopus subject areas

  • Medicine(all)

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