Author: Catharine Paddock PhD, fact checked by Paula Field
Recent research has tied regular use of nonsteroidal anti-inflammatory drugs, such as aspirin, to longer survival in some people with head and neck cancer.
The researchers propose that there should now be a clinical trial to test the effectiveness and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) for this purpose. They suggest that the effect that they observed is likely due to the NSAIDs reducing prostaglandin E2, a molecule that promotes inflammation. A paper on their findings now features in the Journal of Experimental Medicine.
Head and neck cancers are cancers in which tumors develop in the nose, sinuses, larynx, throat, and mouth. In most cases, the tumors arise in the flat thin squamous cells that form the tissue lining of surfaces. For this reason, they bear the name head and neck squamous cell carcinomas (HNSCCs).
In the United States, people with HNSCCs account for around 4 percent of all those with cancer. These types of cancer also tend to have a lower rate of survival compared with many other types. The main risk factors for HNSCC are tobacco use, heavy use of alcohol, sun exposure, and infection with the human papillomavirus (HPV).
Aspirin and HNSCC
Previous research has suggested that taking aspirin regularly can reduce the risk of developing HNSCCs. However, the recent study is the first to link the use of aspirin and other NSAIDs to longer survival in some people who already have HNSCC.
It found that, among people with HNSCC and alterations in the PIK3CA gene, those who regularly used NSAIDs had a longer overall survival rate than those who did not. Regular use of NSAIDs appeared to make no difference to survival in people with HNSCC who did not have any PIK3CA gene alterations.
The researchers defined regular use of NSAIDs as using them at least twice a week for 6 months or longer.
“The present study,” says senior study author Prof. Jennifer R. Grandis M.D., who works in the Department of Otolaryngology at the University of California, San Francisco, “is the first to demonstrate that regular NSAID usage confers a significant clinical advantage in patients with PIK3CA-altered HNSCC.”
PIK3CA and cancer
The PIK3CA gene contains DNA code for the “catalytic subunit” of the signaling enzyme PI3K. The catalytic subunit is the trigger for the enzyme, which activates various signaling reactions in cells. Signals from PI3K are essential for cell survival and activities, such as growth, division, movement, material transport, and protein production. Around 35 percent of people with HNSCC have tumors that harbor “activating mutations” of PIK3CA note the authors.
Colorectal cancer studies have also revealed links between regular NSAID use and improved survival in people who have altered PIK3CA genes. However, they did not explain the underlying mechanism.
Prof. Grandis and colleagues examined medical records and tumor tissue samples belonging to 266 people with HNSCC. The tissue samples came from tumors that surgeons had removed. In most cases, the individuals then received treatment with chemotherapy, or radiotherapy, or both.
Overall survival rose from 45-78 percent
The investigators used the tissue samples to determine which people had altered PIK3CA genes. They then correlated these results against patterns of NSAID use from the medical records.
The analysis revealed that that overall survival increased from 45 to 78 percent in those who regularly took NSAIDs and whose tumors showed that they had an altered PIK3CA gene.
The researchers tested for two types of PIK3CA alterations: mutations and amplifications. They found that the type of alteration did not change the benefit to overall survival. Mutations are alterations in the “spelling” of DNA code, whereas amplification is when DNA sequences repeat. Amplification can lead to increased production of proteins.
The team then tested the effect of NSAIDs on a mouse model. They injected mice with cancer cells containing an altered PIK3CA gene. The mice that received NSAIDs grew much smaller tumors.
NSAIDs block prostaglandin E2 production
Further examination of the mice led the team to suggest that the NSAIDs reduced tumor growth by blocking prostaglandin E2 production.
Prostaglandin E2 has come up in studies of other cancers that have raised the possibility that a PI3K signaling pathway triggers this inflammation-promoting molecule.
The new findings suggest that the benefit of NSAIDs on survival might extend to other types of cancer where there is an altered PIK3CA gene. The discovery about NSAIDs blocking prostaglandin E2 in mice might explain the drugs’ mechanism of action in people with colorectal cancer and altered PIK3CA genes.
Prof, Grandis concludes that they could not make any “specific recommendations” about the use of NSAIDs because of lack of consistency in the dosage, timing, and type of NSAIDs covered by their study.
“But the magnitude of the apparent advantage, especially given the marked morbidity and mortality of this disease, warrants further study in a prospective, randomized clinical trial.”