Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Ovarian cancer subtypes may predict response to bevacizumab

02.06.2014

Molecular sequencing could identify ovarian cancer patients who are most likely to benefit from treatment with bevacizumab (Avastin), a Mayo Clinic-led study has found. Results of the research were presented today at the 2014 American Society of Clinical Oncology Annual Meeting.

The addition of bevacizumab to standard therapy extended progression-free survival more for ovarian cancer patients with molecular subtypes labeled as "proliferative" or "mesenchymal" compared to those with subtypes labeled as "immunoreactive" or "differentiated," says Sean Dowdy, M.D., a Mayo Clinic gynecologic oncologist and senior author of the study. "Though our study is very preliminary, it does suggest that we are getting close to the point where we could use sequencing data to choose more effective and less toxic therapies for patients."

Dr. Dowdy says the U.S. spends about $3 billion a year on bevacizumab for cancer treatment. "Unfortunately, two-thirds of those patients don't respond to the drug, which means we are just giving them toxicity with no benefit. This expression data will help us choose which patients should receive this drug."

Bevacizumab is an angiogenesis inhibitor, a drug that slows the growth of new blood vessels that help cancers grow and spread. An international phase 3 clinical trial known as ICON7 has recently shown that adding this drug to the first-line chemotherapy drugs carboplatin and paclitaxel can improve progression-free survival of ovarian cancer patients.

Dr. Dowdy and his colleagues wanted to determine if the response to this new treatment could be predicted by looking at the molecular makeup of ovarian tumors. First, the researchers used gene expression arrays to analyze biopsies preserved in paraffin-embedded tissue blocks from ICON7 patients.

Then, they used the molecular classification already established by the National Cancer Institute's Cancer Genome Atlas (TCGA) project to separate the patients into four subtypes of the disease, based on precise patterns of genes that had been turned "on" or "off" in their tumors. Of the 359 patients studied, 20 percent had the differentiated subtype, 34 percent had the immunoreactive subtype, 19 percent had the mesenchymal subtype, and 27 percent had the proliferative subtype.

Finally, Dr. Dowdy and his colleagues looked for an association between these molecular subtypes and responses to treatment. They found that patients with the proliferative and mesenchymal subtypes fared the best, with 10.1-and 8.1-month improvements in progression-free survival after treatment with bevacizumab, respectively. In comparison, patients with the immunoreactive and differentiated subtypes only experienced an improvement of 3.8 and 3.7 months, respectively. Similar differences were seen between subtypes when the investigators looked at another measure of treatment response, overall survival.

"It makes sense that patients with proliferative and mesenchymal subtypes would respond the most favorably to bevacizumab, because the same genes and molecular pathways that are implicated in those subtypes are also the ones affected by the drug," says Dr. Dowdy.

Once the rest of the data from the ICON7 trial are published, Dr. Dowdy and his colleagues plan to reanalyze their results to see if even stronger associations can be found between subtypes and outcomes.

They also hope to validate their results in another set of patients, a necessary step before molecular sequencing can identify the patients most likely to respond to this particular drug.

"Right now bevacizumab is not universally used in the first-line treatment of ovarian cancer in the United States because it gives marginal improvement in survival, is extremely expensive at about $100,000 per year, and may have toxic side effects," says Dr. Dowdy. "But if we could identify those patients who will see a 10-month improvement in progression-free survival, it would be worth treating them with the drug. On the other hand, avoiding the use of bevacizumab in patients unlikely to respond will allow us to reduce unnecessary toxicity and prescribe other, potentially more effective drugs for that particular patient."

###

Co-authors include Boris Winterhoff, M.D., Ann Oberg, Ph.D. ,Chen Wang, Ph.D., Shaun Riska, Viji Shridhar, Ph.D., Ellen Goode, Ph.D., and Lynn Hartmann, M.D., all of Mayo Clinic; and S. Kommoss, University of Tübingen, Germany, G.E. Konecny, University of California Los Angeles, J. Fan,Illumina Inc., F. Kommoss,Institute of Pathology, Mannheim, Germany, A. du Bois, Arbeitsgemeinschaft für Gynäkologische Onkologie, Germany,F. Hilpert, Arbeitsgemeinschaft für Gynäkologische Onkologie, Germany,J. Chien, University of Kansas Cancer Center, A.C. Embleton, University College London, U.K., M. Parmar, University College London, U.K., R. Kaplan, University College London, U.K., T. Perren, University of Leeds, U.K. and J. Pfisterer, Arbeitsgemeinschaft für Gynäkologische Onkologie, Germany.

The Mayo Clinic SPORE in ovarian cancer and the Mayo Clinic Cancer Center funded the study.

About Mayo Clinic Cancer Center

As a leading institution funded by the National Cancer Institute, Mayo Clinic Cancer Center conducts basic, clinical and population science research, translating discoveries into improved methods for prevention, diagnosis, prognosis and therapy. For information on cancer clinical trials, call 507-538-7623.

About Mayo Clinic

Recognizing 150 years of serving humanity in 2014, Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit 150 years.mayoclinic.org, http://www.mayoclinic.org/ and newsnetwork.mayoclinic.org.

MEDIA CONTACT:

Joe Dangor, Mayo Clinic Public Affairs, 507-284-5005, newsbureau@mayo.edu

Joe Dangor | Eurek Alert!

Further reports about: Cancer differentiated drugs mesenchymal ovarian subtype subtypes toxic

More articles from Health and Medicine:

nachricht Columbia Engineering team develops targeted drug delivery to lung
03.09.2015 | Columbia University School of Engineering and Applied Science

nachricht Reward, aversion behaviors activated through same brain pathways
03.09.2015 | Washington University School of Medicine

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: Fraunhofer ISE Develops Highly Compact Inverter for Uninterruptible Power Supplies

Silicon Carbide Components Enable Efficiency of 98.7 percent

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE have developed a highly compact and efficient inverter for use in uninterruptible power...

Im Focus: How wind sculpted Earth's largest dust deposit

China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from University of Arizona geoscientists. The study is the first to explain how the steep-fronted plateau formed.

China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from...

Im Focus: An engineered surface unsticks sticky water droplets

The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.

Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...

Im Focus: Increasingly severe disturbances weaken world's temperate forests

Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.

"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...

Im Focus: OU astrophysicist and collaborators find supermassive black holes in quasar nearest Earth

A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.

The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Together - Work - Experience

03.09.2015 | Event News

Networking conference in Heidelberg for outstanding mathematicians and computer scientists

20.08.2015 | Event News

Scientists meet in Münster for the world’s largest Chitin und Chitosan Conference

20.08.2015 | Event News

 
Latest News

Lighter with Laser Welding

03.09.2015 | Process Engineering

For 2-D boron, it's all about that base

03.09.2015 | Materials Sciences

Phagraphene, a 'relative' of graphene, discovered

03.09.2015 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>