The holidays are a time of feasting for many people. You might be thinking fondly right about now of a fantastic meal from last week (prime rib, anyone?) or eagerly anticipating a quiet lunch of leftovers. Not so for cancer patients recovering from chemotherapy. Not only can the treatment lead to nausea, many patients also lose their sense of taste and struggle to eat enough to support their recovery.
Stanford stem cell biologist Philip Beachy, PhD, and instructor Wan-Jin Lu, PhD, wondered about the role of a critical developmental signaling protein called Hedgehog in this loss of taste. Previous work in Beachy's lab showed that the Hedgehog signaling pathway is often misregulated in cancers, and treatment of certain tumors involves specifically blocking the Hedgehog pathway. They published new findings on taste last week in the Proceedings of the National Academy of Sciences.
As Beachy described to me in an email:
Loss of taste sensation occurs in about 85 percent of cancer patients receiving chemotherapy and is a significant clinical issue because it causes loss of appetite, unwanted weight reduction, and complications in recovery. In addition to the widespread loss of taste from traditional cancer therapy, a particularly interesting manifestation of taste disturbance occurs in cancer patients treated with Hedgehog (Hh) pathway antagonists, which our lab discovered and helped develop.
Our sense of taste relies on taste receptor cells clustered in taste buds along our tongues. They're meant to let us know not just when things taste good, but also when something is spoiled or potentially toxic (no, I don't think you can count your cousin's noxious green bean casserole). Due to their role on the frontline of our digestive system, the taste receptor cells undergo a fairly high turnover rate -- dying and being replaced within a period of just a few days or weeks.
These taste receptors relay the taste information they sense to the brain via connections to a cranial ganglion (a cluster of nerve cells behind the ear). But information also flows in the other direction. In fact, it has long been known that the maintenance of the taste receptor cells requires this connection to the ganglion. Why this is hasn't been clear. Beachy and Lu studied laboratory mice to learn that drugs or genetic manipulations that block the response to the Hedgehog signal delivered by the nerves stops the regeneration of taste receptor cells, leading to an eventual die-off of the cells and a loss of taste.
As Lu explained:
We found that sensory organs critically rely on a signal, the Sonic hedgehog (Shh) protein, that is delivered to the tongue epithelium by ganglion neurons that send projections from their cell bodies into the tongue. The pattern of the projections carrying the Shh signal provides spatial guidance for the regeneration of taste organs.
Chemotherapy patients do eventually regain their sense of taste after their treatment is stopped, but it can take several weeks. Beachy and Lu showed that administering drugs that amp up the Hedgehog pathway signaling in mice caused a much more rapid regeneration of the taste receptor cells on the tongue.
"Our findings illustrate a new biological principle, namely, that stable and robust organ patterning in tissues with a high rate of turnover can be specified by neuronal delivery of a regenerative signal to precise locations," Beachy told me. "In addition, our findings suggest that pharmacologic Hedgehog pathway activation may provide a means to accelerate taste recovery in the many cancer patients who lose taste sensation after chemotherapy."
Previously: Viva la hedgehog! Signaling protein also shown to be important in prostate growth, Drug may prevent bladder cancer progression, say Stanford researchers and Humble anti-fungal pill may have a noble side-effect: treating skin cancer
Photo by Ryan Yu