Antipain Agent Shrinks Oral Cancers, Sparing Healthy Tissue


Key Points

  • Capsazepine blocked cancer pain and selectively killed tumor cells in mouse models of oral squamous cell carcinoma.
  • Capsazepine may be a potential therapeutic candidate for oral squamous cell carcinoma.

Mouse models of human oral cancer treated with an agent called capsazepine showed dramatic tumor shrinkage without damage to surrounding tissues, researchers from the School of Dentistry and School of Medicine at The University of Texas Health Science Center at San Antonio found. The findings by Gonzales et al were reported in Oral Oncology.

Oral squamous cell carcinoma is the eighth most common cancer in the United States, with 40,000 new cases and nearly 8,000 deaths reported annually. “These tumors develop primarily on the side of the tongue,” said study first author Cara B. Gonzales, DDS, PhD, Assistant Professor of Comprehensive Dentistry and an investigator with the Cancer Therapy & Research Center at the UT Health Science Center at San Antonio. “Unfortunately, 60% of patients have large tumors before seeking help, and their 5-year survival rate is as low as 30%.”

Study Findings

Capsazepine was developed to block TRPV1, a calcium channel found in pain-sensing neurons. When TRPV1 is activated, a “pain signal” is sent to the brain. Capsazepine may reduce oral cancer pain because it blocks tumor-secreted factors from stimulating TRPV1 on these neurons. Dr. Gonzales found that capsazepine also has anticancer activity that may be associated with its ability to increase oxidative damage in tumors. Enhanced oxidative stress leads to tumor cell apoptosis, the researchers theorized.

“Capsazepine kills cancers selectively, leaving normal tissues alone, and also acts on neurons to block pain, a desirable combination in a potential medication,” Dr. Gonzales said.

So far, only local administration of capsazepine, directly into the primary tumors, has been tested. But many patients with oral cancer have disease that has metastasized. “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.”

Randal A. Otto, MD, FACS, 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.”

Dr. Gonzales is the corresponding author for the Oral Oncology article.

The study was supported by grants from the American Cancer Society, Clinical & Translational Science Awards, and the National Cancer Institute. The University of Texas Health Science Center has claimed intellectual property rights based on results of the study.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.