Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Study Reveals Why Certain Ovarian Cancers Develop Resistance to Platinum-Based Chemotherapy

Published: Wednesday, February 13, 2008
Last Updated: Wednesday, February 13, 2008
Bookmark and Share
Researchers identified a mechanism that explains why some recurrent ovarian tumors become resistant to treatment with commonly used platinum-based chemotherapy drugs.

A team of researchers led by Fred Hutchinson Cancer Research Center has identified a new mechanism that explains why some recurrent ovarian tumors become resistant to treatment with commonly used platinum-based chemotherapy drugs such as cisplatin and carboplatin. They describe their research online Feb. 10 in the journal Nature.

While these findings are based on the study of ovarian-cancer cells from women with inherited mutations in the BRCA2 gene, they also may help explain the mechanics of cisplatin resistance in ovarian-cancer patients with BRCA1-gene mutations. Together such genetic mistakes are thought to cause about 10 percent of ovarian cancers, according to senior author Toshiyasu (Toshi) Taniguchi, M.D., Ph.D.

"Because BRCA1 and BRCA2 have similar functions in terms of DNA repair, we may be able to generalize these findings for women with either mutation," said Taniguchi, an assistant member of the Hutchinson Center's Human Biology and Public Health Sciences divisions.

BRCA2 works to repair damaged DNA; inherited mutations in this gene disrupt that ability, which increases the risk of ovarian and breast cancer. At the same time, such mutations also make cancer cells more vulnerable to DNA-damaging agents such as cisplatin and carboplatin. While ovarian tumors initially respond very well to platinum-based chemotherapy, eventually between 70 percent and 80 percent of advanced-stage ovarian-cancer patients develop a resistance to these drugs.

"The majority of advanced-stage ovarian-cancer patients die due to acquired resistance to platinum-based drugs. It is a serious problem," he said.

Taniguchi and colleagues at the Hutchinson Center, University of Washington, Cedars-Sinai Medical Center and the Mayo Clinic have uncovered how such resistance occurs. They found that when exposed to cisplatin, some ovarian-cancer cells develop secondary mutations on their BRCA2 gene that restore the gene's ability to repair DNA. This restoration of gene function then makes the cancer cells resistant to chemotherapy.

"This event is unlike any previous mechanism of resistance to chemotherapy identified in cancers," said co-author Elizabeth Swisher, M.D., associate professor of medicine in the Department of Obstetrics and Gynecology and director of the Breast and Ovarian Cancer Prevention Program at the University of Washington.

"By identifying the cause of chemotherapy resistance in these cancers, we may be able to better predict who will respond to different chemotherapy agents and find novel ways to re-sensitize tumors to chemotherapy that otherwise would not have had a good response to treatment," Swisher said.

If women with recurrent ovarian cancer are found to have a secondary mutation on their BRCA2 gene, their cancer likely would be resistant not only to platinum-based compounds but also other drugs such as PARP inhibitors. "Testing whether relapsed tumors have a secondary mutation of BRCA2 may be important to predict clinical outcome," Taniguchi said.

The researchers suspect they may be able to generalize their findings regarding secondary mutations in BRCA2 to other DNA-repair genes, such as BRCA1, which may help explain drug resistance to a variety of cancers, including those of the breast, prostate and pancreas.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More Than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Protein-Measurement Technique’s Could Standardize Quantification of the Human Proteome
Novel method could alleviate bottleneck in bringing cancer biomarkers to the clinic and increase reproducibility of pre-clinical research.
Wednesday, December 18, 2013
Gene in Mice Controls Risk-Taking Behavior in Humans
Scientists have studied mice with a single copy of the neuroD2 gene and found they had an impaired ability to form emotional memories and conditioned fear.
Wednesday, September 28, 2005
Scientific News
Criminal Justice Alcohol Program Linked to Decreased Mortality
Institute has announced that in the criminal justice alcohol program deaths dropped by 4.2 percent over six years.
Charting Kidney Cancer Metabolism
Changes in cell metabolism are increasingly recognized as an important way tumors develop and progress, yet these changes are hard to measure and interpret. A new tool designed by MSK scientists allows users to identify metabolic changes in kidney cancer tumors that may one day be targets for therapy.
Improving Regenerative Medicine
Lab-created stem cells may lack key characteristics, UCLA research finds.
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH has announced that decipher the genome of the blacklegged tick which could lead to new tick control methods.
"Dark Side" of the Transcriptome
New approach to quantifying gene "read-outs" reveals important variations in protein synthesis and has implications for understanding neurodegenerative diseases.
Individuals' Medical Histories Predicted by their Noncoding Genomes
Researchers have found that analyzing mutations in regions of the genome that control genes can predict medical conditions such as hypertension, narcolepsy and heart problems.
'Molecular Movie' Opens Door to New Cancer Treatments
An international team of scientists led by the University of Liverpool has produced a 'structural movie' revealing the step-by-step creation of an important naturally occurring chemical in the body that plays a role in some cancers.
New Source of Mutations in Cancer
Recently, a new mutation signature found in cancer cells was suspected to have been created by a family of enzymes found in human cells called the APOBEC3 family.
Advancing Synthetic Biology
Living systems rely on a dizzying variety of chemical reactions essential to development and survival. Most of these involve a specialized class of protein molecules — the enzymes.
Madison Researchers Begin Work on Zika Virus
Work will start with basic questions about Zika virus infection.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!