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- The Tie Between Taste Bud Receptors and Colorectal Cancer
The Tie Between Taste Bud Receptors and Colorectal Cancer
When cancer develops, there is a lot going on behind the scenes. Cells grow and proliferate, disregarding the signals that control cellular growth and death. Cancerous cells manipulate their environment by promoting or tamping down the proteins that positively or negatively affect their growth, respectively. It’s a complex process that scientists are constantly untangling.
Prasad Dandawate, PhD, an assistant professor in the Department of Cancer Biology and a member of The University of Kansas Cancer Center’s Cancer Biology research program, is one of those scientists. A junior investigator, Dr. Dandawate’s research focus came from talking to people with cancer.
A few years ago, visitors to his lab raised the issue of change in taste during cancer treatments. Taste changes are a common side effect of chemotherapy. About half of people undergoing chemotherapy report changes to their taste buds, such as a bitter taste in their mouth. Additional discussions with members of the cancer center’s patient research advocacy program, Patient and Investigator Voices Organizing Together (PIVOT), brought up the same issue. Then a colleague shared a story that really caught his attention.
“His family member had recently died of colorectal cancer,” Dr. Dandawate recalled. “The individual complained of a bitter taste in the mouth before their diagnosis. I was stunned.”
Just keep digging
Dr. Dandawate’s mentors encouraged him to take a closer look. He turned to the National Cancer Institute’s Cancer Genome Atlas, which contains a comprehensive library of cancer genomic profiles. His first search of the database revealed that many cancers have a tie to bitter taste receptors. He then scrutinized each of the 25 bitter taste receptors listed in the library. Only one taste receptor, called Taste Receptor 2 Member 38 (TAS2R38), excessively expresses in people with cancer compared to those without cancer. What’s more, Dr. Dandawate discovered the bitter taste receptor is significantly upregulated in colorectal cancer. When a receptor upregulates, it means it is abnormally expressed at elevated levels compared to normal tissues.
“I kept digging — why was it upregulated in colorectal cancer? What role does taste play in this disease? That’s when it hit me. When this specific taste bud receptor is highly expressed, the odds of surviving colorectal cancer are lower,” said Dr. Dandawate.
Many tests followed. Using the cancer center’s pilot project funds, Dr. Dandawate conducted a tissue microarray containing about 90 samples from colorectal cancer patients. This technique allows for multiple tissue and tumor samples to be analyzed simultaneously. Nearly eight out of 10 patients expressed the bitter taste receptor. Next, Dr. Dandawate needed to determine if the receptor played an active role in cancer development and progression.
I kept digging — why was it upregulated in colorectal cancer? What role does taste play in this disease? That’s when it hit me. Prasad Dandawate, PhD
Calcium signaling is a regulator of pathways important in cancer progression. When a bitter compound binds to taste receptors, it activates and releases calcium. Dr. Dandawate treated colorectal cancer cell lines with the bitter compounds and waited.
“Indeed, I witnessed the calcium release,” Dr. Dandawate said. “That confirmed my hypothesis: the bitter taste receptor overexpresses and plays a functional role in cancer.”
Dr. Dandawate’s preliminary findings resulted in his first-ever grant: a three-year, $400,000 Department of Defense Peer-Reviewed Cancer Development Award. It will fund his work studying how the receptor functions in animal models and colorectal cancer cell lines. If additional studies confirm the taste receptor spurs colorectal cancer growth, scientists may be able to develop targeted therapies. For the 150,000 Americans who will be diagnosed with colorectal cancer this year, it means hope.
The wisdom of listening
After the fortuitous conversations that set him on his research path, Dr. Dandawate understands the power of simply listening. He is now a member of PIVOT and collaborates with advocate Kathy Benich, whose husband died of colorectal cancer. He also works with local organizations that helped provide seed money for his earlier tests.
"Thanks to the support of the Thomas P. O'Sullivan IV Foundation, as well as funds raised by the Rod Rogers Memorial Golf Tournament, I was able to conduct early tests that led me to where I am today,” Dr. Dandawate said. “I’ve met so many people who have been touched by cancer and are dedicated to advancing research to better understand the disease. I have learned so much from their stories.”
Dr. Dandawate added that The University of Kansas Cancer Center’s pilot award funding also helped launch his study. Moreover, Dr. Dandawate is collaborating with Elizabeth Wulff-Burchfield, MD, assistant professor in the Department of Medical Oncology, to study taste perception in muscle-invasive bladder cancer patients who are receiving chemotherapy.
The link between the taste bud receptor and colorectal cancer still intrigues Dr. Dandawate. But cancer is smart. It knows how to use every tool to its benefit. Dr. Dandawate and his team are committed to solving this mystery so better therapies may be developed for colorectal cancer, the second-leading cause of cancer death in the United States.
“What does the taste bud receptor have to do with the colon? A lot, it seems,” Dr. Dandawate said.