Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeting mutant B-Raf protein reduces melanoma development

23.03.2005


Study suggests combination therapy could stop spread, halt growth of melanomas



PA- Researchers at Penn State College of Medicine have identified the mechanism by which the most mutated gene in melanoma, called v599EB-Raf, aids melanoma tumor development demonstrating its importance as a therapeutic target.

"Our studies suggest that using therapies to target and inhibit the function of mutant v599EB-Raf protein could prevent the spread of melanoma and halt tumor growth for those melanomas containing the B-Raf mutation," said Gavin P. Robertson, Ph.D., assistant professor of pharmacology, pathology, and dermatology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center. "With cases of melanoma increasing at about 4 percent per year and no effective treatments available for advanced-stage disease, it’s imperative that we continue to look for important proteins that could be targeted therapeutically. Studies like this one that identify how inhibiting important melanoma regulating proteins reduce melanoma development will lead to a better understanding of the disease, and thus, the development of more effective long-term treatment options for patients."


The study, titled "Mutant V599EB-Raf Regulates Growth and Vascular Development of Malignant Melanoma Tumors," appeared in the March 15, 2005, issue of Cancer Research. The job of normal non-mutated B-Raf is to relay signals from the cell membrane, which is the boundary of the cell receiving the signals, to the nucleus, which contains genetic material and controls many of the cell’s activities. B-Raf is one member of the chain that relays signals playing an important role in cell signaling. The protein is usually only active when needed to relay signals.

In contrast, mutant B-Raf is active all the time, which disrupts the chain’s normal function. Previous studies have shown B-Raf is the most mutated gene in melanomas, present in about 60 percent of human melanomas, but the role mutant B-Raf plays in causing melanoma tumors remained unknown. Robertson used human melanoma cells, applying siRNA, small interfering ribonucleic acids, or BAY 43-9006, a general Raf inhibitor, to show that lowering mutant B-Raf protein reduced melanoma development.

"Reducing B-Raf activity in melanoma cells before tumors had formed significantly decreased the growth potential of the melanoma cells and, in effect, prevented tumor development," Robertson said. "In contrast, reducing B-Raf activity in existing tumors in a mouse model did not shrink the tumors but did prevent them from getting bigger. These discoveries are important for the treatment of metastatic melanoma since therapeutically inhibiting mutant B-Raf could prevent growth of existing tumors and more importantly prevent development of metastatic tumors at secondary sites."

The study shows that in existing melanoma tumors, inhibiting V599EB-Raf activity reduced vascular development, which is essential for tumor growth. Without vascular support the tumors remained the same size. This process occurs by reducing the secretion of VEGF, a factor downstream of B-Raf promoting vascular development, from melanoma cells. "Because the tumors remained the same size, siRNA or BAY 43-9006 would have to be paired with another therapeutic agent to cause the tumors to shrink or disappear," Robertson said.

Of the major types of skin cancer, melanoma is the most metastatic and lethal form. It is currently the seventh most common cancer in the U.S., with about 52,000 cases diagnosed annually. Furthermore, it is the cancer with the second fastest growth rate. In 2004, an American’s lifetime risk of developing melanoma was one in 63 and at the current rate of increase will be one in 50 by 2010. As a direct result of a lack of effective therapeutics, the 2005 prognosis for patients in the metastatic stages of the disease remains very poor with average survival ranging from six to 10 months.

In addition to Robertson, the study team included: Arati Sharma, Nishit R. Trivedi, Melissa A. Zimmerman and Charles D. Smith, Department of Pharmacology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, and David A. Tuveson, University of Pennsylvania.

Valerie Gliem | EurekAlert!
Further information:
http://www.psu.edu

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina 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: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

 
Latest News

Scientists propose synestia, a new type of planetary object

23.05.2017 | Physics and Astronomy

Zap! Graphene is bad news for bacteria

23.05.2017 | Life Sciences

Medical gamma-ray camera is now palm-sized

23.05.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>