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 On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

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: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>