Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mechanisms of acquired chemoresistance in ovarian cancer identified

15.08.2012
The presence of multiple ovarian cancer genomes in an individual patient and the absence or downregulation of the gene LRP1B are associated with the development of chemoresistance in women with the high-grade serous cancer subtype of ovarian cancer whose disease recurs after primary treatment. These study results are published in Cancer Research, a journal of the American Association for Cancer Research.

David Bowtell, Ph.D., head of the Cancer Genomics and Genetic Program at the Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues generated these data in one of the first studies to investigate using patient tumor samples as the mechanisms responsible for the emergence of chemotherapy resistance in high-grade serous ovarian cancer.

"High-grade serous cancers account for about two-thirds of deaths from epithelial invasive ovarian cancer," Bowtell said. "We were interested in identifying the molecular changes that occurred in a tumor between the time when a woman first presented for surgery and chemotherapy, and the time when the tumor recurred and eventually became resistant to chemotherapy."

To examine this, the researchers analyzed metastatic lesions from individual patients and 22 paired pretreatment and post-treatment tumor samples for spatial and temporal genomic variation.

"Spatial variation is a measure of genomic heterogeneity in different deposits of tumor present at primary surgery – variation that the tumor could draw on to evolve over time, especially in the face of chemotherapy," Bowtell explained. "Temporal variation gives us an indication of how much the tumor changes over time, and after one or more lines of chemotherapy."

The researchers compared the level of genomic change among women who were initially chemosensitive and those who were resistant to primary chemotherapy. Tumors that were initially sensitive to chemotherapy but later became resistant evolved further than those tumors that were resistant from the outset. "We were surprised by the extent of variation that was present among the tumor deposits collected at surgery, and by how far the tumors could evolve during therapy," Bowtell said. "The existence of multiple cancer genomes in an individual patient could provide many opportunities for the cancer to circumvent chemotherapy and may help explain why it has been so difficult to make progress with this disease," he said.

The most frequently occurring genomic change found was a deletion and/or downregulation of LRP1B, which encodes a member of a family of proteins that transport lipids into cells. To validate their findings further, the researchers examined the effect of engineering gain or loss of LRP1B in ovarian cancer cell lines. Loss of LRP1B contributed to the emergence of resistance to liposomal doxorubicin, a type of chemotherapy, in women exposed to the drug during their treatment.

"Many women with high-grade serous ovarian cancer experience an excellent response to initial chemotherapy, but unfortunately the disease often returns and becomes resistant to treatment. Currently, we have few tools to predict response to chemotherapy in the relapse setting. LRP1B adds to a handful of other mechanisms so far identified," Bowtell said. "If we can comprehensively map the mechanisms that confer resistance, we may be able to predict whether some women are likely to respond to a certain drug or not, and find ways of reversing resistance."

The study forms part of the International Cancer Genome Consortium (ICGC). Bowtell said that international collaboration is needed to systematically map the emergence of chemotherapy resistance in ovarian cancer and other solid cancers, given that it is difficult to obtain paired pre- and post-treatment samples. He believes that the collection of biopsy tissue in the relapse setting will increasingly be seen as essential for predicting response in the clinic and understanding why treatment failure occurs.

The study was funded by the Association for International Cancer Research.

Follow the AACR on Twitter: @aacr #aacr

Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the AACR

Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR's membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Jeremy Moore | EurekAlert!
Further information:
http://www.aacr.org

More articles from Health and Medicine:

nachricht World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

nachricht Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern

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: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

Leipzig HTP-Forum discusses "hydrothermal processes" as a key technology for a biobased economy

12.07.2017 | Event News

 
Latest News

Researchers create new technique for manipulating polarization of terahertz radiation

20.07.2017 | Information Technology

High-tech sensing illuminates concrete stress testing

20.07.2017 | Materials Sciences

First direct observation and measurement of ultra-fast moving vortices in superconductors

20.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>