A University of Michigan study has identified the pathway responsible for the severe taste disruptions that many patients experience after undergoing chemotherapy to treat basal-cell carcinoma (BCC).
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The study notes that taste buds are extremely susceptible to environmental, metabolic and pharmacologic factors. Previous research has shown that taste-cell function is regulated by the Hedgehog (HH) signaling pathway, which is active in and around taste buds. In contrast to the highly regulated normal functions of HH signaling, however, uncontrolled HH signaling drives the development of BCC tumors. Non-surgical therapy to treat advanced BCC involves drugs that are HH-pathway inhibitors (HPIs) and, while they can help fight off cancer, taste-related side effects can be severe. Indeed, many patients discontinue treatment due to its adverse effect on taste.
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In the new study, researchers explored the theory that taste disturbances in BCC patients result from HPI drug interference with HH signaling in taste organs. Using a mouse model to simulate the effect of HPI-treated patients, the researchers found that blocking the HH signaling pathway led to significant changes in taste-bud structure and function. The authors note that while these changes affected taste responses from the chorda tympani nerve, they did not affect tactile or temperature sensation.
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“Our study establishes an essential and modality-specific requirement for HH signaling in maintaining neurophysiological taste sensation in mice, underlying the likely cause of taste disruption in HPI-treated patients,” the authors wrote. “We propose that taste disturbances in HPI-treated patients derive from HH-dependent loss of taste papilla integrity and taste buds, with a specific, concomitant reduction of peripheral nerve taste responses that transmit taste sensation centrally.”
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Kumari A, Ermilov AN, Allen BL, Bradley RM, Dlugosz AA, Mistretta CM. Hedgehog pathway blockade with the cancer drug LDE225 disrupts taste organs and taste sensation. J Neurophysiol. 2015;113(3):1034-40.