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Under the Microscope: Could Aspirin Enhance Head and Neck Cancer Treatment?

Each year, more than 50,000 people in the U.S. are affected by cancer of the mouth or throat, known as head and neck cancer. Although surgery, chemotherapy and radiation are effective against this type of cancer, these treatments can be disfiguring and affect critical functions like eating, breathing, speaking and smiling.

The V Foundation is helping advance new treatments for head and neck cancer through almost $5 million in research grants. In the last few decades, oral infection with human papillomavirus (HPV) has overtaken tobacco use as the primary cause of these cancers in North America and Europe. Researchers are now focused on understanding how HPV-related head and neck cancers differ from tobacco-related cancers in hopes of developing personalized treatments with fewer long-term side effects.

A conduit from the lab to the clinic

Julie Bauman, MD, chief of oncology at Arizona Cancer Center, is part of a team working to understand the biology of HPV-related cancer. With funding from a V Foundation translational grant, the team performs laboratory and clinical studies that are leading to new breakthroughs in head and neck cancer treatment.

“We want to use insights into the biology of HPV-associated cancers to learn how to apply the right treatment at the right time for the right patient,” said Bauman. “This could reduce treatment side effects and increase the number of cancer survivors while also having a major positive impact on survivors’ quality of life.”

Bauman brings her expertise in clinical trial design to the highly collaborative team, which also includes Jennifer Grandis, MD, who focuses on animal models for head and neck cancer, and Michelle Ozbun, PhD, who specializes in HPV biology. Together, they perform translational studies, meaning that findings in the laboratory are studied or applied in people. They also work in the opposite direction by taking observations from patients and examining them more closely in the laboratory.

“The V Foundation funding has been truly has been transformational for my career,” said Bauman. “And the science that has come from this funding is driving us to explore new tributaries that will reveal even more about head and neck cancer and how best to treat it.”

Aspirin as a personalized treatment

More than half of HPV-associated cancers show mutations in the PIK3CA gene, which codes for a protein involved in cell growth called PI3 kinase. Bauman and her colleagues recently discovered that patients with head and neck cancers featuring these mutations who also took aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) were more likely to survive.

“After making this observation in people with cancer who happened to also be taking an NSAID, we used animal models to uncover the mechanisms at work,” said Bauman. “These experiments showed that the PIK3CA mutations suppress the body’s immune system in a way that produces bad inflammation. However, NSAIDs were able to block this bad inflammation.”

What’s more, the patients seemed to benefit from NSAIDs whether or not their cancer was caused by HPV, suggesting the approach could help a broad population of cancer patients with PIK3CA mutations. To definitively determine whether people with PIK3CA mutations in their cancers uniquely benefit from aspirin, the researchers are planning a placebo-controlled clinical trial.

“If clinical trials are successful, aspirin could be used to not only treat cancer in the United States but would also offer a low-cost and easy-to-access treatment that could be used globally,” said Bauman. “This could have a strong impact in low-and-middle-income countries, where head and neck cancer is rampant and it’s very difficult for people to access state-of-the-art treatments.”

Capitalizing on a window of opportunity

The researchers are also using V Foundation funding to study an experimental drug called BYL719, or alpelisib, by giving the drug to patients with an HPV-related cancer that is scheduled for surgical removal. By comparing tissue from the diagnostic biopsy prior to drug treatment with tissue removed during surgery, this window-of-opportunity clinical trial design will allow the researchers to study how the drug changes the tumor or impacts HPV while also revealing if the drug shrinks the cancer.

“This trial is a tremendous opportunity for us to learn from people with an established cancer whether uniquely targeting the PI3-kinase pathway in HPV-related cancers turns off the gene and all the associated things that that gene is doing to help the cancer grow, spread and to hide it from the body’s defense mechanisms,” said Bauman. In addition to performing clinical trials of the aspirin treatment, the researchers are planning a new window-of-opportunity clinical study to examine how head and neck cancer responds to a drug related to aspirin.