Some cancer patients with aggressive tumors may benefit from anti-inflammatory drugs -
New research raises the prospect that some cancer patients with aggressive tumors may benefit an anti-inflammatory class of drugs used to treat rheumatoid arthritis.
study of triple negative breast cancer, medical school researchers from Saint Louis University of Washington found that some aggressive tumors based on antiviral pathway that seems to drive inflammation, widely recognized for roles in cancer, rheumatoid arthritis and other inflammatory diseases.
tumors that activate this particular antiviral pathway always have dysfunctional forms of p53 and ARF proteins, both encoded by genes known to be highly mutated in various cancers. The researchers found that both genes compensate each other. If both are mutated, the tumors that form are more aggressive than if only one of these genes is lost.
When both genes are lost and antiviral pathway is activated, patients can benefit from an anti-inflammatory class of drugs called JAK inhibitors, currently prescribed for rheumatoid arthritis.
researchers report their results in a recent issue of Cell Reports .
So far, though ARF was known to be expressed in some tumors with mutated p53 ARF was widely considered nonfunctional in this scenario. But investigators have shown that in the absence of p53 ARF actually protects against the formation of a more aggressive tumor.
"It is probably correct to say that completely replaces ARF p53, a tumor suppressor solid with multiple ways of working," said lead author Jason D. Weber, Ph.D., associate professor of medicine. "But it seems that the cell has set up a kind of backup system with ARF. It is not surprising that these are the two most suppressors mutated tumors in cancer. Because they support each other, the most aggressive tumors form when you lose both. "
Weber and his colleagues studied the triple negative breast cancer because these tumors often have mutations in p53 and ARF. Triple negative breast tumors are treated with surgery, chemotherapy and radiotherapy since targeted therapies commonly used against breast cancer with hormone-driven are not effective.
in a search Weber called surprising, the researchers showed that most triple-negative tumors lack p53 and turn ARF on a pathway involved in the innate immune response to viral infection.
"it is not the activation level you would see in a real antiviral response, but it is higher than normal," said Weber . "We are interested in studying whether the antiviral response creates a local inflammatory environment that supports more aggressive tumors."
Weber and his colleagues knew that a family of signaling proteins known as JAK is ahead of the antiviral pathway they showed to stimulate tumor growth.
"There are JAK inhibitors in the use of rheumatoid arthritis and to be tested against a number of other conditions," said Weber. "Our data suggest that these anti-inflammatory drugs may be a way to treat some patients lacking both p53 and ARF."
The drugs potentially could benefit patients in whom both genes are lost, Weber added. If one or p53 ARF is present, this antiviral pathway is not active and therefore not play a role in tumor growth.
Weber and his team are working with experts in the lung, breast and pancreatic cancer to identify patients with mutations in both genes and whether these patients could benefit from JAK inhibitors.
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