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:10/13/2017)... ... ... “The Journey: From the Mountains to the Mission Field”: the story of a ... “The Journey: From the Mountains to the Mission Field” is the creation of published ... all ages and currently teaches a class of ladies at her church, which she ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... Planet Fitness, ... the U.S., announced today its plans to open a flagship location in Covington, LA ... the former Rooms To Go store next to Office Depot in the Holiday Square ...
(Date:10/12/2017)... ... ... Asante, a nationally recognized health system in southern Oregon, ... health joint venture through an agreement, effective October 1, 2017, to create AccentCare ... company with Asante, delivering clinically integrated care, for the past eight years. This ...
(Date:10/12/2017)... ... , ... Leading pediatric oncology experts at Children’s National Health System ... of the International Society of Paediatric Oncology (SIOP) Oct. 12-15. Chaired by ... Blood Disorders at Children’s National, and Stephen P. Hunger, M.D., Chief of the ...
(Date:10/12/2017)... ... , ... In the United States, single-family home owners pay ... York, New Jersey, Massachusetts, Texas, Virginia, Connecticut, and California—the average is $7,000 a ... rates, which contributes to the relatively lower cost of living in places like ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... -- The Rebound mobile app is poised to become a ... of prescription drug addiction. The app empowers users to develop ... down their dosage in a safe, controlled manner while maximizing ... first 100,000 people to sign up will enjoy 3 months ... ...
(Date:9/27/2017)... for their devotion to personalized service, SMP Pharmacy Solutions announces ... the South Florida Business Journal,s 50 Fastest-Growing Companies, and listed ... national specialty pharmacy has found its niche.  To that end, ... honored by SFBJ as the 2017 Power Leader in Health ... his award in October, Bardisa said of the three achievements, ...
(Date:9/25/2017)... 25, 2017  EpiVax, Inc., a leader in ... immune-engineering today announced the launch of EpiVax Oncology ... personalized therapeutic cancer vaccines. EpiVax has provided $500,000 ... to enabling technologies to the new precision immunotherapy ... EpiVax Oncology as Chief Executive Officer. Gad brings ...
Breaking Medicine Technology: