Research to investigate sensitization and activation of “capsaicin receptor” on pain-sensing nerves by cancer mediators, and how these nerves promote cancer progression
NYU Oral Cancer Center has been awarded a five-year, $3.1 million grant (R01 CA231396) by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). The principal investigators, Donna Albertson, PhD, and Brian Schmidt, DDS, MD, PhD, seek to improve oral cancer treatment and alleviate pain by better understanding how a subset of nerves that possess a receptor called TRPV1 on the cell membrane contribute to cancer progression and pain.
Oral cancer patients have a poor prognosis and endure debilitating pain. Albertson and Schmidt have been investigating oral cancer at the molecular level for nearly two decades to address these pressing clinical challenges.
In previous work funded by the NCI, the investigators enrolled patients seen at the NYU Oral Cancer Center in a cancer pain study. They found that some patients reported developing sensitivity to spicy foods, such as chili peppers. The TRPV1 ion channel-sometimes referred to as the “capsaicin receptor”-is activated by the spicy component of chili peppers of the same name. This observation led Albertson and Schmidt to hypothesize that oral cancers release mediators that sensitize and activate nociceptors (pain-sensing nerves) and induce pain. They also postulate that the cancer-primed nociceptors promote cancer growth.
In their newly funded research, which responds to the NCI program focused on the role of the nervous system in regulating or promoting cancer, the investigators will study the sensitization and activation of TRPV1 on nociceptors generated by cancer mediators. They will also study the reciprocal promotion of oral cancer by CGRP-a neuropeptide implicated in pain signaling pathways-released by sensitized and activated nociceptors.
“We propose to study the reciprocal sensory neuron-cancer interaction in relation to cancer promotion and oral cancer pain,” said Albertson, a professor of oral and maxillofacial surgery at NYU College of Dentistry. “The mechanisms of two-way interaction between oral cancer cells and neurons, and how the interactions promote cancer and pain, are not known. There is a critical need to define the mechanism by which oral cancers and neurons interact with each other and the efficacy of disrupting this interaction to treat oral cancer and associated pain.”
“For almost 20 years Donna and I have investigated oral cancer pain and progression,” said Schmidt, a professor of oral and maxillofacial surgery at NYU College of Dentistry and director of the NYU Oral Cancer Center. “This NCI-funded award is the first project in which we combine our respective expertise in cancer biology and neurobiology to reveal how neurons drive cancer growth and cancer pain. This project is an exciting new trajectory for us as we resolve how a subset of nerves contribute to cancer progression and pain. After identifying the components of the cancer-nerve interaction with greater resolution, we seek to develop novel approaches to treat oral cancer and oral cancer pain.”
By exploring the interplay between nerves and cancer, the newly funded research will lay the foundation for developing non-opioid pain therapy as well as cancer treatment. More immediately, the work will pave the way for clinical trials to assess CGRP and CGRP receptor targeted therapies for treating cancer and attenuating cancer pain; these therapies are currently FDA-approved solely for migraine.