A new research has revealed that aggressive cancer tumors may respond to anti-inflammatory drugs that are used to treat rheumatoid arthritis.
Researchers from the Washington University School of Medicine in St. Louis found that some aggressive tumors rely on an antiviral pathway that appears to drive inflammation, and the tumors that activate this 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 tumors that form are more aggressive than if only one of these genes is lost, and when both genes are lost and the antiviral pathway is activated, patients may benefit from a class of anti-inflammatory drugs called JAK inhibitors, currently prescribed for rheumatoid arthritis.
Until now, even though ARF was known to be expressed in some tumors with mutated p53, ARF largely was thought to be nonfunctional in this scenario.
Senior author Jason D. Weber, PhD, explained that it was probably inaccurate to say that ARF completely replaces p53, but it appears the cell has set up a sort of backup system with ARF. It's not surprising that these are the two most highly mutated tumor suppressors in cancer. Because they're backing one another up, the most aggressive tumors form when you lose both.
Weber and his colleagues studied triple-negative breast cancer because these tumors often show mutations in both p53 and ARF. In a finding that Weber called surprising, the researchers showed that most triple-negative tumors lacking p53 and ARF turn on a pathway involved in the innate immune response to viral infection.
Weber said that there are JAK inhibitors in use for rheumatoid arthritis and being tested against a number of other conditions, and their data suggested that these anti-inflammatory drugs may be a way to treat some patients missing both p53 and ARF.
The drugs potentially could benefit patients in whom both genes are lost, Weber added. If either p53 or ARF is present, this antiviral pathway is not active and therefore not playing a role in driving tumor growth.
The findings are published in the journal Cell Reports.
