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 Mobile phone test can reveal vision problems in time
11.02.2016 | University of Gothenburg

nachricht Proteomics and precision medicine
08.02.2016 | University of Iowa Health Care

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: Production of an AIDS vaccine in algae

Today, plants and microorganisms are heavily used for the production of medicinal products. The production of biopharmaceuticals in plants, also referred to as “Molecular Pharming”, represents a continuously growing field of plant biotechnology. Preferred host organisms include yeast and crop plants, such as maize and potato – plants with high demands. With the help of a special algal strain, the research team of Prof. Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam strives to develop a more efficient and resource-saving system for the production of medicines and vaccines. They tested its practicality by synthesizing a component of a potential AIDS vaccine.

The use of plants and microorganisms to produce pharmaceuticals is nothing new. In 1982, bacteria were genetically modified to produce human insulin, a drug...

Im Focus: The most accurate optical single-ion clock worldwide

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...

Im Focus: Goodbye ground control: autonomous nanosatellites

The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.

Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...

Im Focus: Flow phenomena on solid surfaces: Physicists highlight key role played by boundary layer velocity

Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.

The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Im Focus: New study: How stable is the West Antarctic Ice Sheet?

Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels

A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Symposium on Climate Change Adaptation in Africa 2016

12.02.2016 | Event News

Travel grants available: Meet the world’s most proficient mathematicians and computer scientists

09.02.2016 | Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

 
Latest News

LIGO confirms RIT's breakthrough prediction of gravitational waves

12.02.2016 | Physics and Astronomy

Gene switch may repair DNA and prevent cancer

12.02.2016 | Life Sciences

Using 'Pacemakers' in spinal cord injuries

12.02.2016 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>