In some aggressive tumours, patients may benefit from a class of anti-inflammatory drugs called JAK inhibitors, currently prescribed for rheumatoid arthritis, a new research finds.
Studying triple-negative breast cancer, researchers found that some aggressive tumours rely on an antiviral pathway that appears to drive inflammation.
The tumours that activate this particular antiviral pathway always have dysfunctional forms of the proteins p53 and ARF, both encoded by genes known for being highly mutated in various cancers.
The investigators found that the two genes compensate for each other.
If both are mutated, the tumours that form are more aggressive than if only one of these genes is lost.
When both genes are lost and the antiviral pathway is activated, patients may benefit from JAK inhibitors, researchers said.
"There are JAK inhibitors in use for rheumatoid arthritis and being tested against a number of other conditions," said senior author Jason D. Weber from Washington University, St. Louis.
"Our data suggest that these anti-inflammatory drugs may be a way to treat some patients missing both p53 and ARF," he added.
Until now, even though ARF was known to be expressed in some tumours with mutated p53, ARF largely was thought to be non-functional in this scenario.
But the investigators showed that in the absence of p53, ARF actually protects against even more aggressive tumour formation.
"Because they're backing one another up, the most aggressive tumours form when you lose both," Weber explained.
The researchers showed that most triple-negative tumours lacking p53 and ARF turn on a pathway involved in the innate immune response to viral infection.
"The drugs potentially could benefit patients in whom both genes are lost," Weber added.
The study was published in the journal Cell Reports.
