Recent research has tied regular use of non-steroidal 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 non-steroidal 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 tumours develop in the nose, sinuses, larynx, throat, and mouth.
In most cases, the tumours 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).
The main risk factors for HNSCC are tobacco use, heavy use of alcohol, sun exposure, and infection with the human papillomavirus (HPV).
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 signalling enzyme PI3K. The catalytic subunit is the trigger for the enzyme, which activates various signalling 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 per cent of people with HNSCC have tumours that harbour ‘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 tumour tissue samples belonging to 266 people with HNSCC.
The tissue samples came from tumours that surgeons had removed. In most cases, the individuals then received treatment with chemotherapy, or radiotherapy, or both.
Overall survival rose from 45-78 per cent
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 per cent in those who regularly took NSAIDs and whose tumours 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.
NSAIDs block prostaglandin E2 production
Further examination of the mice led the team to suggest that the NSAIDs reduced tumour growth by blocking prostaglandin E2 production.
Prostaglandin E2 has come up in studies of other cancers that have raised the possibility that a PI3K signalling pathway triggers this inflammation-promoting molecule.
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, randomised clinical trial,” Prof Jennifer R. Grandis
Source: Medical News Today
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