Some Cancer Drugs Disrupt Taste by Changing the Cells Inside Taste Buds, Study Shows

A press release from the University of Colorado Anschutz on a study published in Development

Written by David Kelly

Researchers at the University of Colorado Anschutz may have identified why many cancer patients say food suddenly tastes unpleasant during treatment.

The study, published today in Development, found that a class of targeted cancer drugs known as tyrosine kinase inhibitors (TKIs) can change how taste buds are maintained—reducing the ability to taste sweet foods and altering flavor perception overall. While the study was conducted in animal models, researchers believe similar changes likely occur in humans.

The findings offer the clearest explanation to date for a common but often overlooked side effect of cancer treatment.

What researchers found

Using mouse models and lab-grown taste tissue, scientists studied the cancer drug cabozantinib and discovered:

• Taste buds as a whole were not damaged or reduced in number by drug treatment
• The composition of cells inside taste buds shifted
• Drug treatment reduced the number of cells that detect sweet tastes
• Drug treatment increased the number of cells that detect bitter and savory (umami) tastes
• Mice lost their preference for sweet-tasting solutions

Researchers identified an unexpected cause: a protein called KIT.

While TKIs are used to block cancer growth pathways, they also unintentionally block KIT—an important regulator of taste cell development.

When KIT is blocked:

• Sweet-sensing cells fail to develop properly
• Bitter/umami-sensing taste cells take their place

The proportion of sweet and bitter taste bud cells is very tightly controlled. When this proportion is altered, taste perception may drastically change.

“If you lose the sweet component of everything you eat, your entire sense of taste becomes distorted,” said senior author Linda Barlow, PhD, professor of cell and developmental biology at CU Anschutz.

Why it matters

TKIs are important anti-cancer drugs that significantly extend survival in several types of advanced cancers. However, an estimated 10% to 50% of patients taking these drugs experience taste changes, known as dysgeusia.

Though often considered minor, the impact of dysgeusia can be significant:

• Loss of appetite
• Weight loss
• Poor nutrition
• Social withdrawal and reduced quality of life

“It’s difficult for them to enjoy a meal with their family and friends,” Barlow said. “Nothing tastes good to them so they withdraw and become isolated. Isolation leads to depression.”

Study co-author Elaine Lam, MD, professor of medicine and medical oncology at the CU Anschutz Cancer Center, said the drugs are meant to block blood vessels developing in tumors, effectively starving them. Unfortunately, they also cause unintended consequences.

“People don’t eat and they lose weight. This sometimes leads us to reduce or interrupt the dose of their drugs,” said Lam, a kidney cancer specialist. “This research is important because it identifies the underlying mechanisms that affect taste. Now we have to figure out the best way to treat this.”

Lam said possible solutions include designing cancer drugs that avoid blocking KIT or developing treatments to protect taste function.

What’s next

Future research will focus on confirming these findings in patients and identifying ways to prevent or reduce taste changes.

Bottom line

Targeted cancer drugs called tyrosine kinase inhibitors may not destroy taste buds—but they can change their cellular makeup, shifting the balance away from sweet-sensing cells and potentially changing how food tastes.

The study in Development is titled “Tyrosine kinase inhibitors affect sweet taste and dysregulate fate selection of specific taste bud cell subtypes via KIT inhibition”. The lead author is Christina M. Piarowski, PhD. Additional authors are Jennifer K. Scott, Courtney E. Wilson, PhD, Heber I. Lara, PhD, Ernesto Salcedo, PhD, Andrew S. Han, Peter J. Dempsey, PhD and Jakob von Moltke, PhD. The study is available here. 

This press release was originally published on the University of Colorado Anschutz news page.

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