More than 73% of head and neck cancer patients continue to suffer from the chronic consequences of xerostomia months to years after the completion of radiotherapy making this one of the most compelling issues in salivary gland biology. Despite technological advancements in cancer therapies, collateral damage to salivary glands remains a significant problem for these patients and severely diminishes their quality of life. The field of radiation- induced salivary gland damage is severely hampered by the lack of a comprehensive model detailing the molecular stages of damage. The overall vision (long-term goal) is to restore salivary gland function in patients following radiotherapy by identifying healing stages in salivary glands that lead to the stratification and administration of precise therapeutics for their stage. This proposal will integrate metabolic changes at three time points of radiation-induced dysfunction that build a mechanistic foundation to bridge to clinical therapeutic interventions. We hypothesize that changes in salivary gland metabolism enable the loss of function phenotype following radiation treatment of salivary glands. The outcomes from this work include: 1) Metabolic networks that are kinetically altered following IR, 2) Identification of novel regulators of the metabolic phenotype following IR, 3) Linkage of changes in metabolic networks with cellular mechanisms that are involved in the response of salivary glands to IR damage. Understanding this process would have a positive impact by revealing intervention points that promote restoration of salivary gland function.
Radiation is a common treatment in most head and neck cancer cases and results in the long term loss of saliva more than 73% of patients. The resulting lack of salivary gland activity results in significant adverse side effects, which diminish the effectiveness of anti-cancer therapies, and decreases the quality of life for these patients. The long-term goal of this proposal is to understand changes in metabolism in irradiated salivary glands and these studies could have the potential to find new therapies to restore salivary gland function to patients with chronic dry mouth.