A Formidable Foe
Alumna Finding New Treatments for Patients Fighting Oral Cancer
By Ashley Festa
The outlook for oral cancer patients with advanced disease has been grim for decades. But Dr. Cara Gonzales’ promising research may become a new reason for hope.
“People don’t go to the dentist as often as they go to the doctor, and doctors aren’t as accustomed at identifying oral cancer,” said Gonzales, D.D.S., Ph.D., associate professor in the Department of Comprehensive Dentistry. “The dentist is the first person to diagnose oral cancer, so if you don’t go often, it doesn’t get diagnosed until it’s larger. After the cancer has spread, there’s a poor prognosis.”
The prognosis is very poor, in fact. Only about a third of patients will survive if the cancer has spread. It can be difficult, sometimes impossible, to surgically remove oral tumors because there are so many critical structures in the head and neck that can be damaged during an operation. As for drugs, there have been no new effective therapies for these patients for more than 40 years. Dr. Gonzales is working on several studies that could become new treatment options.
The first she hypothesizes will have few or no side effects for patients, unlike other treatments, such as chemotherapy. The treatment works by selectively targeting cancer cells and leaving healthy cells untouched. Cancer cells divide faster than normal cells, so they need more energy, requiring the mitochondria—the cell’s powerhouse—to work overtime. Because they divide rapidly, cancer cells release more free radicals, but they also create more antioxidants, which keeps them alive. This delicate balance between free radical production and antioxidant capability may be exploited to selectively kill cancer cells. Dr. Gonzales is studying a drug that causes them to create so many free radicals that the cells die. Because the drug acts only on the rapidly dividing cancer cells instead of non-cancerous cells, Dr. Gonzales doesn’t anticipate as many side effects as current chemotherapies, which do not selectively target the tumor.
Her research has been successful with lab mice, and she’s trying to secure funding to move to larger animal studies. She hopes to begin clinical trials with patients within five years.
Dr. Gonzales’ second focus is developing a new therapeutic strategy using two drugs that are already FDA approved: an anaplastic lymphoma kinase (ALK) inhibitor and an epidermal growth factor receptor (EGFR) inhibitor. EGFR inhibitors have been used in oral cancer patients with little efficacy. Dr. Gonzales has shown that the combination of these drugs significantly reduces tumor growth in mouse models. She is currently developing a clinical study evaluating potential side effects and toxicities of this novel drug combination in oral cancer patients. The ALK inhibitor is already in use to treat lung cancers that make too much of the ALK protein due to genetic mutations. Dr. Gonzales has shown in oral cancer, however, that the ALK gene is not mutated, but it is activated in the wrong place—the oral cavity. The ALK gene isn’t normally “on” in the mouth, so patients’ tumors can be screened for the abnormality. People with positive results have a higher chance of the tumor metastasizing, and they may be candidates for clinical trials in the future. Dr. Gonzales hopes that since the FDA has already approved both drugs, she’ll be able to begin clinical trials soon.
In addition to her research, Dr. Gonzales works with students at the dental school’s Center for Oral Health Care & Research.
“UT Health sees the most patients for head and neck cancer in South Texas,” she said, “so what better place to study oral cancer?”