Navigation Links
Study reveals why certain ovarian cancers develop resistance to platinum-based chemotherapy
Date:2/10/2008

SEATTLE 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 Centers 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 genes 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.

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.


'/>"/>

Contact: Kristen Woodward
kwoodwar@fhcrc.org
206-667-5095
Fred Hutchinson Cancer Research Center
Source:Eurekalert

Related medicine news :

1. Penn study finds pro-death proteins required to regulate healthy immune function
2. New study shows promise in reducing surgical risks associated with surgical bleeding
3. Study, meta-analysis examine factors associated with death from heatstroke
4. Study suggests loss of 2 types of neurons -- not just 1 -- triggers Parkinsons symptoms
5. Study says COPD testing is not measuring up
6. Preclinical study suggests organ-transplant drug may aid in lupus fight
7. Ability to cope with stress can increase good cholesterol in older white men, study finds
8. High alcohol consumption increases stroke risk, Tulane study says
9. Mailman School of Public Health study examines link between racial discrimination and substance use
10. Pitt study finds inequality in tobacco advertising
11. Stanford study highlights cost-effective method of lowering heart disease risks
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/29/2016)... ... May 29, 2016 , ... Whole Health Supply is happy to announce the ... available via Amazon.com. This new style of nail clipper has a wider jaw opening ... approximately 4mm and the actual handle is 2.5mm thick to accommodate the cutting force. ...
(Date:5/28/2016)... ... ... May 26, 2016- In search of the K. Warriors, Shaolin Institute is ... Warriors” on June 4, 2016 at Ashbury Hotel and Suites 600 West Interstate 65 ... by Shaolin Institute and sanctioned by KSF (Kungfu Sanda Federation), This is the 28th ...
(Date:5/27/2016)... Newark, NJ (PRWEB) , ... May 27, 2016 , ... ... been named as YWCA Tribute to Women and Industry (TWIN) 2016 honorees. The ... to their workplace. For this year, Geri Boone, Director of the MLTSS (Managed Long-Term ...
(Date:5/27/2016)... ... May 27, 2016 , ... ... installment is bolstered by inspiring human-interest stories, courtesy of awareness-driven celebrities and thought ... industry, from leading advocates, associations and industry leaders such as Bioness. , ...
(Date:5/27/2016)... (PRWEB) , ... May 27, 2016 , ... ... in scholarships to students studying complementary medicine. Allison Outerbridge is this year’s ... her award on May 18 at the university’s Student Leadership Awards ceremony. , ...
Breaking Medicine News(10 mins):
(Date:5/27/2016)... May 27, 2016 LabStyle Innovations ... Diabetes Management Tool, today announced that the Company,s Chief Financial ... MicroCap Conference being held June 1-2 in New ... held June 7-9 in Los Angeles, CA. ... recent corporate and operational milestones, including the U.S. FDA Clearance ...
(Date:5/27/2016)... TEL-AVIV, Israel , May 27, 2016 /PRNewswire/ ... KTOV), an innovative biopharmaceutical company focused on late-stage ... by Dexcel Pharma of pivotal batches ... Food and Drug Administration (FDA). This follows Kitov,s ... pivotal Phase III trial successfully met its primary ...
(Date:5/26/2016)... York , May 26, 2016 ... Research "Medical Waste Management Market - U.S. Industry Analysis, Size, ... waste management market in the U.S. was valued at US$ ... a CAGR of 3.4% from 2015 to 2023 to reach ... exhaustive analysis of current and emerging needle free drug delivery ...
Breaking Medicine Technology: