Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Some aggressive cancers may respond to anti-inflammatory drugs

30.06.2014

New research raises the prospect that some cancer patients with aggressive tumors may benefit from a class of anti-inflammatory drugs used to treat rheumatoid arthritis.

Studying triple-negative breast cancer, researchers at Washington University School of Medicine in St. Louis found that some aggressive tumors rely on an antiviral pathway that appears to drive inflammation, widely recognized for roles in cancer, rheumatoid arthritis and other inflammatory diseases.


Raleigh Kladney

A mouse mammary gland missing the tumor suppressor p53 shows expression of ARF (green), now known for a backup role in protecting cells from becoming cancerous. If both p53 and ARF are mutated, the tumors that form are aggressive and may benefit from treatment with anti-inflammatory drugs called JAK inhibitors, currently prescribed for rheumatoid arthritis.

The tumors 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 tumors 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 a class of anti-inflammatory drugs called JAK inhibitors, currently prescribed for rheumatoid arthritis.

The investigators report their findings in a recent issue of the journal Cell Reports.

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. But the investigators showed that in the absence of p53, ARF actually protects against even more aggressive tumor formation.

“It’s probably inaccurate to say that ARF completely replaces p53, which is a robust tumor suppressor with multiple ways of working,” said senior author Jason D. Weber, PhD, associate professor of medicine. “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. Triple-negative breast tumors are treated with surgery, chemotherapy and radiation since targeted therapies commonly used against hormone-driven breast cancers are not effective.

In a finding 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.

“It’s not the level of activation you would see in a true antiviral response, but it’s higher than normal,” Weber said. “We are interested in studying whether this antiviral response is creating a local environment of inflammation that supports more aggressive tumors.”

Weber and his colleagues knew that a signaling protein family known as JAK is upstream of the antiviral pathway they showed to be driving tumor growth.

“There are JAK inhibitors in use for rheumatoid arthritis and being tested against a number of other conditions,” Weber said. “Our data suggest 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.

Weber and his team are collaborating with specialists in lung, breast and pancreatic cancer to identify patients with mutations in both genes and to find out whether such patients might benefit from JAK inhibitors.

This work was supported by the National Institutes of Health (NIH), the National Cancer Institute (NCI) of the NIH, a Clinical and Translational Science Award (CTSA) from the NIH and a Department of Defense Era of Hope Scholar grant. Grant numbers R01CA120436, 1K12CA167540, UL1RR024992, and 5T32GM007067.

Forys JT, Kuzmicki CE, Saporita AJ, Winkeler CL, Maggi Jr. LB, Weber JD. ARF and p53 coordinate tumor suppression of an oncogenic IFN-beta-STAT1-ISG15 signaling axis. Cell Reports. April 2014.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Julia Evangelou Strait | Eurek Alert!
Further information:
https://news.wustl.edu/news/Pages/27051.aspx

More articles from Health and Medicine:

nachricht Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>