Researchers from the School of Dentistry and School of Medicine at The University of Texas Health Science Center at San Antonio have found that capsazepine, a type of vanilloid antagonist, dramatically reduces the size of oral tumors without affecting the surrounding tissues.
Oral squamous cell carcinoma (OSCC) is responsible for 8,000 annual deaths in the US alone, with 40,000 new cases being reported every year and with a concerning death rate of approximately 57%.
“These tumors develop primarily on the side of the tongue,” said the study lead author Cara B. Gonzales, D.D.S., Ph.D., assistant professor of comprehensive dentistry and a researcher at the Cancer Therapy & Research Center at the UT Health Science Center at San Antonio. “Unfortunately, 60 percent of patients have large tumors before seeking help, and their five-year survival rate is as low as 30 percent.”
The team developed three mouse xenograft models to investigate the mechanisms of vanilloid cytotoxicity and anti-tumor effects in OSCC.
Capsazepine is significantly cytotoxic to tumor cells upon treatment and it specifically blocks TRPV1, a calcium channel found in pain-sensing neurons that upon activation triggers a pain signal to the brain. This drug seems to act by blocking tumor-secreted factors from stimulating TRPV1 on these neurons, thus reducing tumor pain. Furthermore, the team also found that in vivo, intra-tumoral injections of capsazepine were extremely effective in suppressing tumor growth, while displaying minimal toxicities.
This anti-cancer activity may be associated with capsazepine’s capacity to increase oxidative damage in tumors, such as the generation of reactive oxygen species (ROS), as oxidative stress leads to the apoptosis of tumor cells.
“Capsazepine kills cancers selectively, leaving normal tissues alone, and also acts on neurons to block pain, a desirable combination in a potential medication,” said Dr. Gonzalez.
Even though only intra-tumoral administration of capsazepine has been tested, many patients have metastatic oral cancer, urging the need for a general administration strategy. “We would like to be able to deliver this therapy systemically to target metastatic disease,” Dr. Gonzales said. “Our laboratory is working with the Center for Innovation in Drug Discovery, a partnership between the Health Science Center and UTSA, to develop novel drugs that are similar to capsazepine with improved efficacy for the purpose of systemic administration to treat tumors that are inaccessible to local injection or that have metastasized.”
These studies demonstrate capsazepine as a potential therapeutic candidate for OSCC, hoping to minimize the elevated death percentage associated with this type of tumors.
Randal A. Otto, M.D., F.A.C.S., professor and chairman of the Department of Otolaryngology-Head & Neck Surgery in the School of Medicine, said: “These tumors, if identified and treated early, are definitely curable. Unfortunately, most patients present with advanced disease with the cancer involving critical structures. This markedly decreases the chance for cure and dramatically increases the risks associated with treatment. Anything that selectively attacks the tumor while not injuring the normal tissues can only help the patient.”
This work was published in the journal Oral Oncology, and was funded by the American Cancer Society Mentored Research Scholar Grant, the Clinical & Translational Science Award (CTSA) Grant, the National Cancer Institute P30 Grant to the Cancer Therapy & Research Center at the UT Health Science Center at San Antonio, with The Health Science Center claiming intellectual property on results of the study.