Cancer therapy-related salivary dysfunction

Abstract

Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described.

Figure 1. Schematic of the various physiological roles saliva is critical in supporting.

Summary of saliva’s contributions to various physiological and behavioral functions. Changes in saliva production or the chemical makeup of saliva as seen in xerostomia can negatively affect all of these aspects of a patient’s life, decreasing overall quality of several facets of the patient’s life.

Figure 2. Salivary gland anatomy.

(A) Location of major salivary glands (yellow) in the human are displayed in two projections. The lower left inset shows the general glandular structure, depicting serous acini, mucinous acini, myoepithelial cells, and ducts. To the right of the inset, pie charts convey differences in the mucous and serous composition of the major salivary glands. (B) Minor salivary glands are widely dispersed throughout the oral cavity, as indicated by yellow regions. The inset represents the structure of minor salivary glands, which consist of single seromucinous acini draining directly into excretory ducts.

Figure 3. Effects of cancer therapies on the salivary glands.

(A) Acute and chronic responses to cancer treatment are associated with fibrosis and damage to salivary acini, including changes to endothelial and myoepithelial cells as well as serous and mucous epithelial cells. Recent studies have indicated a role for T cell activation and other indicated changes in immunotherapy-related salivary dysfunction, while macrophages have been shown to be involved in damage response following radiotherapy. (B) Timeline of known effects of radiotherapy, chemotherapy, and immunotherapy on salivary glands. Solid bars represent approximate start and end time of indicated changes; a dashed bar indicates presumed changes. Gray wedge indicates the decline of overall incidence of these responses in patients over time. Effects of radiotherapy have been well described; however, few descriptions of mechanisms underlying chemotherapy or immunotherapy-driven changes have been described. Adapted from Jasmer et al. (20).