Penn researchers have successfully identified a new pathway to activate apoptosis in head and neck squamous cell carcinoma and are now turning their attention to launching a clinical trial designed around this science in the coming year.
The breakthrough follows on the heels of another by the same group, led by Ryan M. Carey, MD, Assistant Professor of Head and Neck Oncology and Microvascular Reconstructive Surgery at the Perelman School of Medicine at the University of Pennsylvania, and Robert J. Lee, PhD, Assistant Professor of Otorhinolaryngology at the Perelman School of Medicine. Their team was the first to identify taste receptors on head and neck cancer cells.
The expression of bitter taste receptors had already been reported in several other types of cancer, including breast, ovarian, prostate, and colorectal cancers.
“This is an emerging field, and our group is the first to be looking at these receptors in head and neck cancer, specifically,” Dr. Carey says.
About 900,000 cases of head and neck cancers are diagnosed worldwide each year. In the United States, head and neck cancers account for about three to four percent of all cancer diagnoses. Most often, the patient will identify an abnormality themselves that will lead to the diagnosis, Dr. Carey says. “They may have a lesion in their mouth or a new mass forming on their neck, or they’ve suddenly developed difficulty swallowing or talking.”
Tumors in the head and neck region can be “very challenging to treat,” Dr. Carey adds. His experience as a surgeon has informed his pursuits as a researcher. “I really want to help advance our ability to treat these tumors,” he says. “There’s so much work to be done on this front. But I’m even more motivated since we found this novel target that could potentially make a big difference in the treatment of our patients.”
Taste receptors, of course, are associated with the tongue, but are prevalent throughout the body, where they perform a variety of biological actions. They are one of many classes of G-protein coupled receptors, which are often expressed on the surface of a cell, where they bind to external molecules and activate intracellular processes. Bitter taste receptors, for instance, sit on the surface of tastebuds and bind to bitter tasting compounds within bitter foods and drinks. This binding capacity leads to a signal transduction that allows you to perceive that taste, Dr. Carey says.
With regard to oncology, taste receptors have a number of diverse functions. For example, bitter taste receptors enable the cancer cells to interact with the tumor’s microenvironment. Those found on the surface of immune cells can regulate phagocytosis, and taste receptors found on the surface of head and neck cancer cells have been found to regulate proliferation, observes Dr. Carey.
Bitter Taste Receptors as Targets for Cancer Therapy
“Bitter taste receptors have emerged as an interesting and novel target,” says Dr. Carey. “So far, we’ve been able to establish that they’re associated with survival outcomes, and that we can potentially target them in the treatment of head and neck cancers.”
A part of Dr. Carey’s research involves bitter tasting compounds, which are everywhere, including commonly used medications. Dr. Carey and his team experimented with one such medication and were able to activate apoptosis in the cancer cells. They’re now designing a clinical trial that they expect to launch in the coming year with the goal of leveraging these taste receptors as biomarkers or therapeutic targets for treating malignancies.
Given their recent findings, the future is brimming with potential.
“Head and neck cancers are unique because they’re generally in accessible locations,” Dr. Carey says, “so you could easily inject around a tumor, or have someone use a bitter oral rinse. Either way might be able to trigger this beneficial response.”
He’s also interested in exploring the genetics behind this response. A number of genes are responsible for the expression of particular taste receptors, which naturally raises questions like, if someone has nonfunctional bitter taste receptors, do they have a higher risk of cancer? Or would they respond differently to cancer?
“With that information, we may be able to predict someone’s response to treatment,” notes Dr. Carey.
There are also unanswered questions around the bitter taste receptors’ interaction with the surrounding environment. Is there an interplay between the cancer cells and immune cells that’s being facilitated and mediated by the taste receptors on both?
“Wherever those answers land, it’s clear this is worth all of our attention right now,” Dr. Carey says. We really feel like we’re actively translating this to help our patients. Our hope is that within five to 10 years we can appreciate a positive result from this and then actually make changes based on it.”
To help that day arrive sooner rather than later, Dr. Carey and his team have been strategically repurposing bitter tasting compounds that have already been approved by the Food and Drug Administration. The decision has likely shaved years off the timeline and helped invoke the sense, in Dr. Carey’s lab that a breakthrough is on the horizon.