SAN ANTONIO (Sept. 2, 2016) — A multidisciplinary research team at the UT Health Science Center San Antonio has found a new way to treat deadly, late-stage head and neck cancer, reducing tumor size in mouse models by 50 percent in just 14 days.
Results were seen in both human cancer cells and in human tumors developed in mice. Cara Gonzales, D.D.S., Ph.D., of the School of Dentistry led the study, published in the August edition of Oral Oncology.
Ninety percent of head and neck cancers are squamous cell carcinoma. Individuals with late-stage squamous cell carcinoma of the head and neck have a five-year survival rate as low as 34 percent. Traditionally, this type of cancer has been treated with a combination of surgery, radiation and/or chemotherapy.
New research aimed at developing targeted chemotherapy for squamous cell carcinoma has focused on a protein called the epidermal growth factor receptor (EGFR), which is found at high levels in more than 80 percent of head and neck squamous cell cancers. Unfortunately, EGFR- targeted treatments have been clinically unsuccessful.
Study combines two targets for treatment
Nameer B. Kirma, Ph.D., from the Department of Molecular Medicine at the UT Health Science Center, discovered a role for the anaplastic lymphoma kinase (ALK) in oral cancers that metastasize. ALK is highly expressed in other cancer types, such as non-small cell lung cancer. Therapies targeting ALK have been successful in treating those tumor types.
Together, Dr. Kirma and Dr. Gonzales an assistant professor in the Department of Comprehensive Dentistry, expanded these studies to test the effectiveness of ALK inhibitors in head-and-neck-cancer mouse models developed in Dr. Gonzales’ lab. They found that treatments targeting EGFR alone slowed the tumor growth rate, but the tumors continued to grow. Treatments that targeted ALK alone had little anti-tumor effect, but when combined to also target EGFR, the tumors shrank in size by 50 percent in the 14-day test period. No adverse side effects were noted in the animals.
Dr. Gonzales explained, “ALK and EGFR use the same pathway to drive tumor growth. Therefore, targeting only one of these receptors does not completely block their shared pathway. Imagine two lanes of traffic merging. You would have to put up a roadblock across both lanes in order to completely stop the flow of traffic. We believe that blocking both ALK and EGFR effectively eliminates their ability to signal to the cells to grow and spread to other parts of the body.”
Human trials on the horizon
“Given that both drugs are FDA approved, we hope to move this novel targeted therapy into a clinical trial soon. ALK inhibitors have never been tested against head and neck cancers,” Dr. Kirma said. The research group is applying for grants to fund clinical trials.
The UT Health Science Center research team also includes Jorge De La Chapa, research assistant in the Department of Comprehensive Dentistry; Pothana Saikumar, Ph.D., associate professor of research in the Department of Pathology; Prajjal Kanti Singha, a postdoctoral fellow in Pathology; Nicholas Dybdal-Hargreaves, joint D.D.S./Ph.D. student; Jeffery Chavez, senior research associate in the Department of Biochemistry; Aaron Horning, a Ph.D. student in Molecular Medicine; and Jamie Parra, research assistant in Pathology.
The study was supported by the UT Health Science Center San Antonio; the UT Health Science Center’s Cancer Therapy & Research Center (CTRC); the Experimental and Developmental Therapeutics Pilot Award and the William and Ella Owens Medical Research Foundation Cancer Research Pilot Award. Immunohistochemistry was performed by the CTRC Core Pathology Laboratory supported by the National Cancer Institute’s Cancer Center Support Grant (P30 CA054174). http://dx.doi.org/10.1016/j.oraloncology.2016.05.007
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