ReviewInsight in taste alterations during treatment with protein kinase inhibitors

- Patient-reported taste alterations are a commonly reported side-effect of protein kinase inhibitors (PKIs).
- The underlying pathobiology is unknown and it has never been established whether an objective taste dysfunction develops.
- Hypothesized mechanisms include oral toxicity and altered taste or smell perception.
- These factors should objectively be assessed to unravel the pathobiology, needed for development of potential treatment options.

The role of Protein Kinase Inhibitors (PKI) in the treatment of various types of cancer is increasingly prominent. Their clinical application is accompanied by the development of side effects, among which patient-reported taste alterations. These alterations are missed frequently, but impair nutritional intake, are associated with weight loss and often result in significant morbidity, especially in the context of chronic administration. Accurate reporting of taste alterations is hampered by lack of modules for symptom objectification and inadequate understanding on the underlying mechanisms. In this review we initially describe the physiology of taste and smell and the mechanism of action of PKIs. We proceed to summarize taste related side effects as reported in major clinical trials and describe possible causal factors. Lastly, an in-depth analysis is given on potential molecular pathways responsible for the PKI-induced taste alterations. Objectification of patient-reported symptoms and universal reporting, along with a better understanding of the underlying mechanisms, will lead to early recognition and optimized treatment, ultimately improving patient adherence and quality of life.