Potential Therapies for Oral, Head and Neck Cancers

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by Andy Evangelista

Andrei Goga, MD, PhD (inset), is applying his research on breast cancer (cells, pictured) to head and neck cancer. *Source: National Cancer Institute*

As a cancer scientist, Andrei Goga, MD, PhD, fixates on genes that disrupt the cell cycle and drive tumor growth. He has conducted laboratory studies in worms, fish and mice.

But Goga widens his research lens and focuses straight into the clinic. “As a medical oncologist, I’ve seen too many patients die of cancer,” he said.

Goga, professor in the School of Dentistry’s Department of Cell and Tissue Biology, has investigated for more than 20 years how certain oncogenes signal and alter cells, creating intricate pathways for tumorgenesis.

He started that research as a postdoctoral fellow in the laboratory of UCSF Chancellor Emeritus and Nobel Laureate J. Michael Bishop, who pioneered studies of the role of oncogenes in cancer. Goga started his own lab in 2007 and recently identified new therapeutic strategies to target oncogenes that play a role in aggressive tumors, including in lung, liver and breast cancer. All the while, he taught students and treated cancer patients at UCSF.

Goga now broadens his studies and co-directs a new School of Dentistry research program in oral, head and neck cancer.

And on June 21, he was honored and officially named the Dr. Arnold and Dianne Gazarian Presidential Chair in Dentistry. The professorship will help support Goga’s cancer research in the Department of Cell and Tissue Biology.

Housing the research in the School of Dentistry is practical, scientifically and clinically. “What we’ve learned in liver and breast tumors is applicable to other tumors, including those in the head and neck,” said Goga.

Head and neck cancer accounts for about 4 percent of all cancers in the U.S. An estimated 65,000 people in the U.S. will be diagnosed with the cancer this year, and it will kill more than 13,000 people, according to data from the American Cancer Society and the National Cancer Institute.

Moreover, dentists play a key role in screening for that cancer, as they are trained to detect symptoms such as lumps and sores in the head, neck or mouth; difficulty swallowing and hoarseness in the voice.

Building collaborations

For the oral, head and neck cancer research program, Goga and co-director Patrick Ha, professor and the chief of head and neck oncologic surgery in the Department of Otolaryngology, have built a collaborative group of 17 experts from the schools of Dentistry and Medicine. They are basic scientists and clinicians from various disciplines — ranging from immunology and endocrinology to radiation oncology and pathology — who share their knowledge.

They hold seminars, on topics such as tumor progression, the possible impact of nerves on head and neck cancer and biomarkers and chemoprevention for the disease.

Researchers in the group have a common goal: to understand the basic mechanisms of cancer and bring their insights and new therapies to the clinic.

Goga has set the bar. In a study published last fall, his laboratory team identified a new drug target for triple-negative breast cancer (TNBC), an often-deadly cancer. Conventional chemotherapy fails to eradicate this particular breast cancer because it metastasizes early and rapidly, and it is not treatable with modern hormonal therapies.

Targeting the culprit: MYC

Goga’s study centered on a specific oncogene, MYC (pronounced “mick”). MYC is implicated in many aggressive cancers, and Goga has found highly-elevated levels of MYC in TBNC tumors.

Because of its physical characteristics and its fundamental role in normal cellular function, MYC had long been considered an “undruggable” protein. Pharmaceutical companies for decades have been unsuccessful in targeting MYC.

But Goga and his team employed an approach to undruggable proteins known as “synthetic lethality,” which involves discovering the other proteins upon which these pharmacologically intractable proteins crucially depend to drive cancer growth.

So, shutting down the activity of responsible proteins becomes a viable strategy in developing drug therapies.

“The next step is to figure out how to bring these findings into early-phase clinical trials with patients, and we’re partnering with pharmaceutical companies to explore this," said Goga.

The research on TNBC is applicable to head and neck cancer, as MYC is amplified in 35 percent of squamous cell head and neck cancers, he said.

Goga’s lab also has identified metabolic pathways and compounds that reverse MYC signaling. So, research is underway to find other drug targets.

These studies are exciting because researchers can now go after these oncogenes and tumor-driving processes specifically and wherever they are in the body, said Goga. “And that’s the name of the game.”