Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Drug may slow spread of deadly eye cancer

29.11.2011
A drug commonly used to treat seizures appears to make eye tumors less likely to grow if they spread to other parts of the body, according to researchers at Washington University School of Medicine in St. Louis.

Their findings are available online in the journal Clinical Cancer Research.


A look at aggressive uveal melanoma cells under the microscope. These tumor calls carry the so-called "class 2 signature," meaning they are likely to be aggressive and spread outside of the eye. J. William Harbour, MD

Uveal melanoma, the second most common form of melanoma, can be very aggressive and spread, or metastasize, from the eye to other organs, especially the liver.

“Melanoma in general, and uveal melanoma in particular, is notoriously difficult to treat once it has metastasized and grown in a distant organ,” says principal investigator J. William Harbour, MD. “We previously identified an aggressive class 2 molecular type of uveal melanoma that, in most cases, already has metastasized by the time the eye cancer is diagnosed, even though imaging the body can’t detect it yet. This microscopic amount of cancer can remain dormant in the liver and elsewhere for several years before it begins to grow and becomes lethal.”

Once this happens, the prospects for survival are poor, according to Harbour, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences and professor of cell biology and of molecular oncology. He also directs the Center for Ocular Oncology at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

Harbour’s new study shows that drugs known as histone deacetylase (HDAC) inhibitors alter the conformation of the DNA of the aggressive form of uveal melanoma, which changes the way key genes are expressed, rendering the tumor cells less aggressive.

“We looked at uveal melanoma cells in the laboratory and in an animal model, and we found that HDAC inhibitors can block the growth and proliferation of tumor cells,” he says. “HDAC inhibitors appear to reverse the aggressive molecular signature that we had identified several years ago as a marker for metastatic death. When we look at aggressive melanoma cells under the microscope after treatment with HDAC inhibitors, they look more like normal cells and less like tumor cells.”

Because HDAC inhibitors already are on the market, Harbour says he thinks it may be possible to quickly begin testing the drugs in patients with aggressive forms of uveal melanoma.

The drugs have relatively mild side effects that are not as severe as those seen in patients undergoing chemotherapy. One HDAC inhibitor, for example, is the anti-seizure drug valproic acid. Its most common side effect is drowsiness, which is typical of all HDAC inhibitors.

Clinical trials of HDAC inhibitors could begin in the next six to 12 months, Harbour says. Already, other researchers have applied for funding to begin testing an HDAC inhibitor called SAHA (suberoylanilide hydroxic acid) in patients with metastatic uveal melanoma.

“I think this is a reasonable place to start in the challenging effort to improve survival in patients with metastatic uveal melanoma,” Harbour says. “I suspect that the best role for HDAC inhibitors will be to slow or prevent the growth of tumor cells that have spread out of the eye but cannot yet be detected. This might lengthen the time between the original eye treatment and the appearance of detectable cancer in the liver and elsewhere.”

Like the chicken pox virus that lives for years in nerve cells without affecting health, Harbour says treatment with HDAC inhibitors may allow patients with aggressive melanomas to live for many years without any detectable spread of their disease.

Harbour and his colleagues previously developed a screening test to predict whether the cancer would be likely to spread to the liver and other parts of the body. The test is helpful because although less than 4 percent of patients with uveal melanoma have detectable metastatic disease, up to half will eventually die of metastasis even after successful treatment of the tumor with radiation, surgery, or, in the worst cases, removal of the eye.

Tumors that tend to remain contained within the eye are called class 1 uveal melanomas. With a needle biopsy, doctors can quickly determine whether a tumor is likely to be a class 1 cancer or whether it carries a molecular signature that identifies it as a high-risk, class 2 melanoma. Harbour’s team developed a test to identify the class 2 molecular signature, and that test is now being used around the world to detect the aggressive form of uveal melanoma.

In addition, Harbour’s team published a paper last year in the journal Science identifying a mutation in a gene called BAP-1 that helped further explain why some eye tumors develop the class 2 signature and acquire the ability to spread. Harbour explains that HDAC inhibitors appear to reverse some of the effects of BAP-1 mutations on the melanoma cell.

Landreville S, Agapova OA, Matatall KA, Kneass ZT, Onken MD, Lee RS, Bowcock AM, Harbour JW. Histone dacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clinical Cancer Research, available online at: doi:10.1158/1078-0432.CCR-11-0946

Funding for this research comes from a Fonds de la Recherche en Sante du Quebec Postdoctoral Training Award, the Alvin J. Siteman Cancer Center Summer Undergraduate Research Fellowship program, and the National Cancer Institute, the National Eye Institute the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health (NIH), and by the Horncrest Foundation and Research to Prevent Blindness.

J. William Harbour and Washington University may receive income based on a license of related technology by the university to Castle Biosciences Inc. This study was not supported by Castle Biosciences Inc.

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 fourth 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.

Caroline Arbanas | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Health and Medicine:

nachricht Finnish research group discovers a new immune system regulator
23.02.2018 | University of Turku

nachricht Minimising risks of transplants
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

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: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>