HPV-positive head and neck cancer is driven by HPV – a virus that is well known to cause cervical cancer. HPV-positive head and neck cancer is typically treated with surgery, radiation, and/or chemotherapy. However, treatment outcomes are far from ideal, and there is a clear need for new therapies. This cancer features a viral protein called E6 as a lynchpin of its survival and growth. Previous research has shown that using genetic tools to block this protein can prevent tumor growth. E6, and the signaling pathways associated with it, may therefore represent a tantalizing therapeutic target for HPV-driven cancers. Read More
To investigate this further, Dr. Wendi Quinn O’Neill of the University Hospitals Seidman Cancer Center and colleagues examined the relationship between HPV-positive head and neck cancer, the E6 protein, and pre-existing drugs that could modulate related signaling pathways. Their goal was to find better ways to treat the cancer.
The researchers first used a genetic tool to block the production of E6 in cancer cells, and observed increased levels of cell death and reduced cell growth. The researchers then tested this in mice and observed significant reduction in tumor size when E6 production was blocked, with a 90% reduction in some mice.
Genetic tools are not always suitable for use in patients, so the team wished to find a drug that can block the activity of E6. They investigated the biochemical signaling pathways that are affected by the E6 protein, and then searched for existing drugs that are known to affect those pathways. This approach is known as drug repurposing. It has additional benefits because the safety profiles of existing drugs are already established.
The researchers identified an FDA-approved drug called fenofibrate, which is used to treat abnormal levels of blood lipids. Fenofibrate modulates several signaling pathways that are also affected by genetic manipulation of E6 in cancer cells. This drug is much less harmful than the conventional chemotherapy drugs used to treat head and neck cancer.
Initially, the researchers tested the effect of fenofibrate on head and neck cancer cells in a dish, and found that it successfully reduced cell growth and survival. When the researchers proceeded to mouse studies, they found that fenofibrate reduced tumor growth as much as cisplatin – the ‘standard-of-care’ chemotherapy drug for head and neck cancer patients.
When the researchers combined fenofibrate with cisplatin, they observed tumor-killing effects that were greater than that of either drug alone. In half of the mice that received the combined treatment, the tumor had almost completely disappeared, with one mouse showing no evidence of the tumor after treatment.
These results are very promising, and the research team is moving to evaluate fenofibrate in a ‘window-of-opportunity’ phase 1 clinical trial for HPV-positive head and neck cancer.
