Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New subtype of ovarian cancer may be vulnerable to anti-angiogenic drugs

15.02.2012
Scientists at Dana-Farber Cancer Institute have identified a subtype of ovarian cancer able to build its own blood vessels, suggesting that such tumors might be especially susceptible to "anti-angiogenic" drugs that block blood vessel formation.

In a study published in the online journal PloS ONE, the investigators estimate that the subtype may account for a third of all serous ovarian cancers, a common cancer of the surface of the ovaries. The discovery of the subtype, made by analyzing data from the clinical records of more than 1,500 serous ovarian cancer patients and samples of their tumors, may spur clinical trials to determine if patients with the subtype can benefit from anti-angiogenic therapies now being tested in other cancers.

"Unlike breast cancer, where we can distinguish different subtypes based on their genetic signatures, ovarian cancer has been viewed as a monolithically homogenous disease -- each tumor very much like every other," says John Quackenbush, PhD, the study's co-senior author with his Dana-Farber colleague Ursula Matulonis, MD. "With this study, we've shown that serous ovarian cancer exists in at least one distinct subtype at the molecular level, raising the possibility that it will be vulnerable to therapies directed at its molecular weaknesses."

Ovarian cancer is the fifth leading cause of cancer death for women in the United States, responsible for more than 15,000 deaths annually in this country, according to the American Cancer Society. High grade serous ovarian cancers – the focus of the current study – are one of several varieties of tumors that appear in the "epithelial" tissue lining the ovaries. Epithelial tumors account for about half of all ovarian cancers. ("Serous" refers to tumors that are found in tissues that produce a serum-like fluid. "High grade" refers to the highly abnormal appearance of the tumor's cells under a microscope.)

Although many ovarian cancers initially recede or grow more slowly when treated with conventional, platinum-based chemotherapy drugs, the vast majority overcome that tendency and begin to grow again.

In the current study, researchers scanned the activity of thousands of genes in high grade serous ovarian cancers from 129 patients with an advanced stage of the disease. They then sifted the data using an algorithm called rISIS, which randomly assigns the tumor samples to different groups until it finds a grouping with a distinct set of genetic characteristics. That grouping represents a potential cancer subtype.

The technique yielded four possible subtypes of high grade serous ovarian cancer, but only one of them held up when researchers applied a different technique for scanning gene activity. When researchers catalogued the genes that were particularly active -- or "highly expressed" -- in that single subtype, a key trend appeared: many of the genes were known to be involved in angiogenesis, the process by which tumors build blood vessels to tap into the bloodstream for oxygen and nutrients. This distinctive array of overactive genes was dubbed the "angiogenesis signature."

A common shortcoming of gene-profiling studies is that the results often aren't reproducible: different labs obtain different gene signatures for the same types of cancer. To ensure their findings were not skewed by their lab procedures or testing methods, the Dana-Farber investigators analyzed data from ten published, independent studies of gene expression in serous ovarian cancer. Together, these studies involved 1,606 ovarian cancer patients.

"The analysis confirmed our finding," Quackenbush relates. "The angiogenic [blood vessel-producing] subtype is real." When investigators analyzed the medical records of those 1,606 patients, they found that those with the angiogenic subtype tended to have more advanced, aggressive tumors than those without the subtype.

A clinical trial will be necessary to determine if angiogenesis-blocking drugs are particularly effective in patients with the angiogenic subtype. But there is reason for optimism: about 30 percent of serous ovarian cancer patients who receive angiogenesis inhibitors in a clinical trial benefit from the drugs; and the angiogenic subtype comprises about 30 percent of all serous ovarian cancers. "It is a test like this that may in the future help us select which patients will benefit most from a drug like Avastin," says Matulonis.

The researchers believe that their classification of this new subtype has great potential to influence the treatment many patients receive and improve outcomes for a significant number of people with this disease. "The approach we've taken in this study offers a powerful way of identifying molecular subtypes of other cancers as well," says Quackenbush.

The first authors of the study are Stefan Bentink, PhD, and Benjamin Haibe-Kains, PhD, of Dana-Farber and the Harvard School of Public Health. Co-authors include Thomas Risch, Kristina Holton, and Renee Rubio, of Dana-Farber; Joyce Liu, MD, and Aedin Culhane, PhD, of Dana-Farber and the Harvard School of Public Health; Ronny Drapkin, MD, PhD, of Dana-Farber and Brigham and Women's Hospital; Jian-Bing Fan, PhD, Craig April, PhD, Jing Chen, and Eliza Wickham-Garcia, of Illumina, Inc., of San Diego; and Michelle Hirsch, MD, PhD, of Brigham and Women's.

The study was supported by the Dana-Farber Cancer Institute Women's Cancer Program, the Strategic Plan Fund, and the Madeline Franchi Ovarian Cancer Research Fund at Dana-Farber.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center and it provides pediatric care with Children's Hospital Boston as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter: @danafarber or Facebook: facebook.com/danafarbercancerinstitute

Bill Schaller | EurekAlert!
Further information:
http://www.dana-farber.org

More articles from Health and Medicine:

nachricht Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

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: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>