It takes two
Two weeks is all it took for deadly, late-stage head and neck tumors to shrink in mouse models. The cause: a combination of two targeted treatments already approved by the Food and Drug Administration.
Ninety percent of head and neck cancers are squamous cell carcinoma. Individuals with late-stage cancer 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.
Nameer B. Kirma, Ph.D., associate professor of molecular medicine, discovered a role for anaplastic lymphoma kinase (ALK) in oral cancers that metastasize. Therapies targeting ALK have been successful in treating those tumor types, as well as other cancer types such as non-small cell lung cancers.
Dr. Kirma and Cara Gonzales, D.D.S., Ph.D., assistant professor of comprehensive dentistry, began testing the effectiveness of ALK inhibitors in head-and-neck cancer mouse models. They found when they combined the therapies, the tumors shrank by 50 percent in a 14-day test period.
Results were seen in both human cancer cells and in human tumors developed in mice. No adverse side effects were noted. Both proteins use the same pathway to drive tumor growth, Dr. Gonzales said.
“Targeting only one of these receptors does not completely block their shared pathway,” she said. “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.”
The researchers are now applying for grants to move the therapy into clinical trials.
The study was published in Oral Oncology.