Tyrosine kinase inhibitors affect sweet taste and dysregulate fate selection of specific taste bud cell subtypes via KIT inhibition.
Christina M Piarowski, Jennifer K Scott, Courtney E Wilson, Heber I Lara, Ernesto Salcedo, Andrew S Han, Elaine T Lam, Peter J Dempsey, Jakob von Moltke, Linda A Barlow
Article in Development (Cambridge, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3citing papers in PubMed
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Christina M PiarowskiDepartment of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jennifer K ScottDepartment of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Courtney E WilsonDepartment of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Heber I LaraDepartment of Immunology, University of Washington, Seattle, WA 98109, USA.
Ernesto SalcedoDepartment of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Andrew S HanDepartment of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Elaine T LamDepartment of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.ORCID 0000-0001-5629-3402
Peter J DempseyDepartment of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jakob von MoltkeDepartment of Immunology, University of Washington, Seattle, WA 98109, USA.ORCID 0000-0003-2894-3353
Linda A BarlowDepartment of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.ORCID 0000-0001-7998-2219
Funding
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Mechanisms of Adult Taste Bud RegenerationR01DC012383 · NIDCD · UNIVERSITY OF COLORADO DENVER · PI BARLOW, LINDA A · 2012 to 2021
$3.4M
Regulation of the tuft-ILC2 circuit in the small intestineR01AI167923 · NIAID · UNIVERSITY OF WASHINGTON · PI Jakob H. von Moltke · 2022 to 2026
$2.8M
Characterization of progenitor populations in adult taste epitheliumR01DC018489 · NIDCD · UNIVERSITY OF COLORADO DENVER · PI BARLOW, LINDA A · 2020 to 2024
$2.5M
Predoctoral Training in the Genetics of Development, Disease and RegenerationT32GM141742 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Bruce H Appel, Jeffrey Kyle Moore · 2021 to 2026
$1.9M
The role of Kit signaling in taste bud regenerationR01DC021865 · NIDCD · UNIVERSITY OF COLORADO DENVER · PI Linda A Barlow · 2024 to 2026
$1.8M
Use of lingual organoids to screen for the impact of targeted cancer therapies on taste bud renewalR21CA236480 · NCI · UNIVERSITY OF COLORADO DENVER · PI BARLOW, LINDA A · 2019 to 2020
$372k
Not so sweet: Investigating the role of c-Kit in sweet cell homeostasisF31DC020634 · NIDCD · UNIVERSITY OF COLORADO DENVER · PI PIAROWSKI, CHRISTINA M · 2022 to 2024
Taste dysfunction, or dysgeusia, is a common side effect of many cancer drugs. Dysgeusia is often reported by people treated with anti-angiogenic tyrosine kinase inhibitors (TKIs), which inhibit receptor tyrosine kinases (RTKs). However, the mechanisms by which TKIs cause dysgeusia are not understood, as the role of RTKs in adult taste homeostasis is unknown. Here, we find that treating adult mice with the TKI cabozantinib shifts the fate of differentiating functional taste cell subtypes within taste buds. Through behavioral assays, we find this cell fate shift leads to blunted responses to sweet tastants in cabozantinib-treated mice. Finally, we show that inducible knockout of the RTK KIT, which is inhibited by cabozantinib, phenocopies taste cell fate shifts induced by TKI treatment. Our results establish KIT as a regulator of taste cell homeostasis and suggest that KIT inhibition may underlie TKI-induced dysgeusia in humans.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.
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