Novel agents have potential to break 40-year drought in oral cancer drug development
SAN ANTONIO (June 3, 2019) ― Researchers at UT Health San Antonio have identified a potent new class of anti-cancer drugs that target oral cancer cells while leaving other cells unharmed. The new drug class also has shown promise in stopping other types of cancer.
In two recent papers, a research team led by Cara Gonzales, D.D.S., Ph.D., developed a new class of drugs broadly referred to as capsazepine analogs and tested them against oral and other types of cancers in preclinical and animal studies.
Low survival rate for advanced and recurrent oral cancer
“Our main goal was to develop cancer-targeting drugs to effectively treat advanced and recurrent oral cancer,” said Dr. Gonzales, an associate professor in the School of Dentistry’s Department of Comprehensive Dentistry. “This is important because oral cancer is a deadly disease with a five-year survival rate of only 40 percent,” she said. “Oral cancer is rarely diagnosed in its earliest stages when it can be cured. About 75 percent of patients come to the clinic with advanced disease, dramatically lowering their chance of survival,” she said.
The team’s previous research showed that capsazepine is a potent cancer killer. Capsazepine is a synthetic cousin of capsaicin, the substance in chili peppers that gives them their heat. While studying oral cancer pain, Dr. Gonzales’ team discovered that capsazepine has significant cancer-fighting activity through a cancer-selective mechanism of action. In collaboration with the Center for Innovative Drug Discovery, a partnership of UT Health San Antonio and The University of Texas at San Antonio, more potent capsazepine analogs were developed with significantly stronger anti-cancer efficacy in mouse models of oral cancer and no adverse effects on healthy tissue.
Two papers show progress
In a paper published in Bioorganic & Medicinal Chemistry in November, Dr. Gonzales’ team describes their work synthesizing 30 new compounds whose chemical structures were based on the parent compound, capsazepine. The compounds were then screened based on their ability to kill oral cancer cells in culture. Lead compounds CIDD24, CIDD99 and CIDD111 were validated in mouse models of human cancer.
This data informed additional preclinical and animal work outlined in the second paper, published in March in the Journal of Oral Pathology & Medicine. These studies zeroed in on the most effective lead compound, CIDD99. This compound eradicated the tumors while leaving normal healthy tissue unaffected. An added benefit was that CIDD99 also sensitized oral cancer cells to traditional chemotherapies, meaning that much lower doses of chemotherapy could be used with dramatically greater effectiveness and fewer side effects.
Drugs effective against other types of cancer
CIDD99 was also effective against a panel of other cancer types and therefore may provide a new therapy for multiple cancers with fewer side effects than traditional chemotherapies. “As we got further into our research, we found that CIDD99 also is effective against non-small-cell lung cancer, triple-negative breast cancer and prostate cancer cells,” Dr. Gonzales said.
“These results are very exciting because no new drugs have been developed in over 40 years to treat oral cancer. While immunotherapy works very well, it is only effective in a small group of patients. Our compounds may provide a new class of drugs that may be effective for all oral cancer patients,” she added.
Patents filed on three drugs
UT Health San Antonio and UTSA have a patent on the three drugs through the Office of Technology Commercialization, which serves both universities as a catalyst for stimulating innovation and entrepreneurship among faculty, staff and students and industry partners through the UT System.
Researchers working toward human clinical trials
The research team is now working with venture capital companies to apply for Small Business Technology Transfer grants and an American Cancer Society Mission Boost Phase 1 grant to conduct additional preclinical studies that are required before applying to the U.S. Food and Drug Administration for an Investigational New Drug (IND) status. An IND designation authorizes the administration of an experimental agent in humans enabling future clinical trials.
“These grants will help us generate additional data regarding safety, toxicity and how they work in the body that will get us ready to submit our FDA application for human trials,” Dr. Gonzales said.
The research was supported by an Institute for Integration of Medicine and Science Clinical and Translational Science Pilot Award and a San Antonio Life Science Sciences Institute Center for Innovative Drug Discoveries Pilot Grant.
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