Anti-inflammatory drugs may defeat a treatment-resistant type of cancer

June 24, 2009
Anti-inflammatory drugs may defeat a treatment-resistant type of cancer
Irene Pedersen’s translational research has revealed a potential new treatment for a form of lymphoma. Photo courtesy Irene Pedersen.

(PhysOrg.com) -- Effective drugs for treating a chemotherapy-resistant form of lymphoma might already be on the market according to a study that has pieced together a chemical pathway involved in the disease.

By following the trail of several molecular flags that mark this type of cancer, a team from the University of California, San Diego, the Burnham Institute for Medical Research and the University of Copenhagen Hospital have discovered that anti-inflammatory drugs used to treat arthritis will shrink lymphoma tumors in mice.

Their report, published in the July issue of the journal EMBO Molecular Medicine, also strengthens evidence for a link between inflammation and cancer.

"If this shows promise with early clinical experiments, the treatment would be immediately available," said Michael David, a professor of biology who leads the group at UC San Diego.

The research focused on a type of non-Hodgkin lymphoma called diffuse large B-cell lymphoma. In some patients with the disease, chemotherapy works well. In a recent study of 40 patients more than 75 percent of patients with one form of this type of lymphoma survived five years or longer.

But that study also identified a group of patients whose cancer proved difficult to treat. Their tumors failed to respond to chemotherapy, and only 16 percent of patients with this form of lymphoma survived more than five years after they were diagnosed.

Several molecular flags mark this treatment-resistant lymphoma, but the links between them were unknown until now. The new paper reports that isolated from these patients have depressed levels of a protein called SHIP1, which was known to suppress tumors. In fact, patients with the lowest levels of SHIP1 are the least likely to survive.

The resistant type of lymphoma cells also have elevated levels of miR-155, a specific example of a type of called microRNA, the team found. They demonstrated that miR-155 suppresses SHIP1 by sticking to the template for the protein, preventing its manufacture.

This raised the possibility that these patients might respond favorably to a treatment that interrupted that pathway. "It makes sense to block that loop," said Irene Pedersen, a research scientist in the Division of Biological Sciences at UC San Diego and lead author of the paper.

The final clue came from earlier reports that an inflammatory molecule called TNFα could boost levels of miR-155. Additional laboratory work confirmed the observation for this type of lymphoma cell.

"Our study strengthens the scientific link between inflammation and tumor progression," David said. "The prevailing thought is that you need two mutations to get cancer. But it might take just one mutation plus inflammation."

The anti-inflammatory drugs etanercept and infliximab, which are currently used to treat arthritis and inflammatory bowel disease, work by suppressing TNFα, suggesting a new way to curb the malignancy of this type of lymphoma.

The team tested the idea in mice that had been injected with aggressive lymphoma cells and found that nascent tumors shrank in six days.

"It's a promising result of this whole translational path," said Pedersen, whose initial training was in cancers of the blood. "To get somewhere we had to study the mouse models and the molecular profiles. I hope it will be beneficial to patients."

Patients with that has not responded to chemotherapy and who are ineligible for a bone-marrow transplant will be the first to receive the new treatment. The team in Copenhagen has begun recruiting for an initial clinical study.

Source: University of California - San Diego (news : web)

Related Stories

Recommended for you

Major study of genetics of breast cancer provides clues to mechanisms behind the disease

October 23, 2017
Seventy-two new genetic variants that contribute to the risk of developing breast cancer have been identified by a major international collaboration involving hundreds of researchers worldwide.

Big Data shows how cancer interacts with its surroundings

October 23, 2017
By combining data from sources that at first seemed to be incompatible, UC San Francisco researchers have identified a molecular signature in tissue adjacent to tumors in eight of the most common cancers that suggests they ...

Symptom burden may increase hospital length of stay, readmission risk in advanced cancer

October 23, 2017
Hospitalized patients with advanced cancer who report more intense and numerous physical and psychological symptoms appear to be at risk for longer hospital stays and unplanned hospital readmissions. The report from a Massachusetts ...

CAR-T immunotherapy may help blood cancer patients who don't respond to standard treatments

October 20, 2017
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is one of the first centers nationwide to offer a new immunotherapy that targets certain blood cancers. Newly approved ...

Researchers pinpoint causes for spike in breast cancer genetic testing

October 20, 2017
A sharp rise in the number of women seeking BRCA genetic testing to evaluate their risk of developing breast cancer was driven by multiple factors, including celebrity endorsement, according to researchers at the University ...

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.