Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Salk Researchers Find New Drug Target for Lung Cancer

Drugs targeting an enzyme involved in inflammation might offer a new avenue for treating certain lung cancers, according to a new study by scientists at the Salk Institute for Biological Studies.

The scientists discovered that blocking the activity of the enzyme IKK2, which helps activate the body's inflammation response, slowed the growth of tumors in mice with lung cancer and increased their lifespan.

The findings, reported February 12 in Nature Cell Biology, suggest that drugs that hinder the ability of the enzyme to command cellular activity might prove effective as lung cancer therapies.

"Lung cancer is one of most lethal cancers and prognosis for patients is often poor, with only about 15 percent surviving more than 5 years," says Inder Verma, Salk's American Cancer Society Professor of Molecular Biology and lead author of the paper. "We developed a new method of initiating lung cancer in mice, which has properties associated with human lung cancer, and used this model to identify the role of this enzyme in cancer proliferation. We believe that this research could one day lead to therapies that improve the outlook for lung cancer patients."

Scientists have long known that there is a link between cancer and inflammation, the body's first line of defense against infection. Some of the same biochemical players that protect the body by controlling the inflammation response of cells can also be hijacked by genetic mutations involved in the development of cancer.

To better understand how these normally helpful components of the immune system are put to nefarious tasks in cancer cells, Verma and his colleagues developed a new method of inducing non-small-cell lung cancer in mice. This type accounts for as much as 80 percent of all lung cancer cases.

The researchers used a modified virus to insert genetic mutations into cells lining the mice's lungs, causing the animals to develop tumors. This laid the groundwork for studies on the molecular causes of this specific cancer type that would be impossible in humans.

They then turned their attention to a protein complex, NF-KB, that initiates the inflammation response to infection by orchestrating a cell's genetic activity. Malfunctioning regulation of NF-KB has been linked to various types of cancer, including lung cancer, but due to its many functions in the cell, drugs that directly target NF-KB would likely cause severe side effects.

To get around this limitation, the Salk researchers focused on IKK2, an enzyme that spurs NF-KB's activity in response to stress. When they blocked IKK2 activity in the mice with lung cancer, the mice had smaller tumors and lived longer, suggesting that the enzyme is necessary for NF-KB to stimulate tumor growth.

"Now that we understand IKK2 is required for NF-KB to promote tumor growth, we hope to find ways to target its activity with drugs," says Yifeng Xia, a postdoctoral researcher in Verma's lab and first author on the paper. "Systemically and chronically blocking IKK2 activity is too toxic to be used in chemotherapy, but we might be able to target another molecule in the signaling pathway by which IKK2 regulates tumor growth."

The researchers also showed that Timp-1, a gene involved in regulating cell growth, carries orders from NF-KB to tell lung cancer cells to proliferate. When they suppressed the expression of the gene, the mice with lung cancer had smaller tumors and survived longer.

"The next step is to develop antibodies or other types of drugs that can neutralize Timp-1 to abolish its pro-proliferation role in lung cancer," says Xia.

The Salk scientists now hope to develop a mouse model of small cell lung cancer, a more aggressive form of the disease that's been linked to smoking. They will then test whether the potential drug targets they discovered in this study would be relevant for this more deadly cancer.

The other authors on the paper were Reuben J. Shaw, a professor in Salk's Molecular and Cell Biology Laboratory; Salk postdoctoral researcher, Narayana Yeddula, and pathologist, Mathias Leblanc; Eugene Ke, of University of California, San Diego; and Yonghui Zhang and Eric Oldfield, of the University of Illinois at Urbana-Champaign.

The study was funded by the Ellison Medical Foundation, H.N. and Frances C. Berger Foundation, Ipsen/Biomeasure, Sanofi Aventis, Leducq Foundation, National Institutes of Health, Merieux Foundation, Prostate Cancer Foundation and the U.S. Department of Defense.
About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.

Andy Hoang | Newswise Science News
Further information:

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>