Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Tumor target suggests personalized treatment for melanoma

Identification of a key player in a signaling pathway involved in the development of melanoma – the deadliest form of skin cancer – may offer hope for new targeted melanoma therapies.

Ann Richmond, Ph.D., and colleagues at Vanderbilt-Ingram Cancer Center report that a signaling molecule, known as IKKâ, is essential for melanoma tumor development in a mouse model of the disease. The results, published June 7 in the Journal of Clinical Investigation, also point to ways of targeting therapies that inhibit IKKâ toward the patients most likely to benefit from them based on their genetic profile.

Melanoma is the deadliest form of skin cancer and incredibly difficult to treat successfully once the tumor has spread beyond the skin.

Prior studies have shown that the NF-êB signaling pathway – centered on the protein NF-êB, which regulates gene expression – is abnormally activated in tumor cells; the pathway is turned "on" constantly, even at times it should be turned "off." This activation often results from abnormal activation of another enzyme in the pathway, IKKâ.

Just how NF-êB contributes to tumor progression has been unclear. And with drugs that inhibit this pathway entering clinical trials, a clearer picture of its function in tumor progression is needed.

To better understand the role of this pathway – in particular, of IKKâ's role – Richmond's lab developed a mouse model that mimics the genetic alterations involved in melanoma development in humans.

Jinming Yang, Ph.D., a staff scientist in Richmond's lab, led the effort to generate these mice, which lack the tumor suppressor INK4a/ARF (commonly lost in melanomas) and have the Ras/Raf pathway activated (which is activated in about 70 percent of melanoma lesions).

The researchers then added the ability to "turn off" IKKâ only in melanocytes, the pigment-producing skin cells in which melanomas initiate, simply by treating the mice with an antibiotic.

Mice with normal IKKâ activity developed "loads and loads of melanoma tumors all over their bodies…on the tail, the ear, and anywhere melanocytes are," said Richmond, an Ingram Professor of Cancer Biology at Vanderbilt University Medical Center and a senior career research scientist with the Department of Veterans Affairs.

But mice in which IKKâ was "turned off" developed no melanoma tumors.

They also found that treating mice with normal IKKâ activity with small molecule inhibitors of the enzyme could inhibit the growth of melanoma lesions.

"This shows for the first time that you have to have IKKâ for Ras-induced melanoma, suggesting that there's a way to specifically target melanoma lesions," she said.

However, the experiments identified an important caveat: blocking IKKâ only seemed to protect against melanoma formation when another tumor suppressor, p53, is expressed.

Since mutations that disrupt p53 are sometimes found in melanomas, this suggests that therapies targeting IKKâ or the NF-êB pathway in general would need to be limited to tumors with normal p53.

Richmond cautions, "With NF-êB inhibitors entering clinical trials at this time, it is imperative that these data be taken into consideration for patient selection or evaluation of response in these trials."

Richmond is collaborating with Vanderbilt-Ingram Cancer Center investigators Mark Kelley, M.D., and Jeffrey Sosman, M.D., to identify, in human tumor samples, which tumors would respond to targeted inhibitors of the Ras/Raf and NF-êB pathways.

Such information could aid in diagnosis and "be used to deliver personalized medicine" to melanoma patients in the future, she said.

"We're passionate about (IKKâ inhibitors) possibly going forward, maybe not as a single agent, but in combination (treatments). As we are able to better predict which patients will respond to which drugs, there's real hope there."

Richmond is also a professor of Medicine in the Division of Dermatology. Other authors on the study include: Ryan Splittgerber, Ph.D., Fiona Yull, D.Phil., Sara Kantrow, Gregory Ayers from Vanderbilt, and Michael Karin, Ph.D., from the University of California San Diego. The research was supported by the Department of Veterans Affairs, the National Institutes of Health, the Skin Disease Research Center and the Vanderbilt-Ingram Cancer Center.

Dagny Stuart | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

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: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>