Navigation Links
Study reveals why certain ovarian cancers develop resistance to platinum-based chemotherapy

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
Fred Hutchinson Cancer Research Center

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:
(Date:11/27/2015)... ... November 28, 2015 , ... There is only one major ... billings from last year? , This question has not been an easy question to ... the retirement age and the younger workforce don’t share the same discipline around working ...
(Date:11/27/2015)... ... November 27, 2015 , ... A team of Swiss doctors has released a ... Mesothelioma has just posted the findings on the website. Click here to read ... of 136 mesothelioma patients who were treated with chemotherapy followed by EPP surgery. Among ...
(Date:11/27/2015)... , ... November 27, 2015 , ... ProSidebar: Fashion ... Final Cut Pro X. With ProSidebar: Fasion, video editors can easily add an ... as a minimalist title opener. Utilize presets featuring self-animating drop zones, lines, bars, ...
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... ... failing. Secura Consultants has prided itself for not only fulfilling the needs of ... protection solutions at an affordable price and providing top-tier customer service. However, there's ...
(Date:11/27/2015)... ... November 27, 2015 , ... Avid collector, Andrew Hawley from Vintage Rock ... concert posters. This is one of Joplin's most famous and beautiful concert posters. The ... of Michigan in Ann Arbor. The According to Hawley, "It is hard to believe ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... 2015 --> --> ... to find optimal contrast weighting of MRI for patients ... signed a research agreement with SyntheticMR in order to use ... it is possible to generate multiple contrast images from a ... has left, thus making it possible to both fine tune ...
(Date:11/26/2015)... November 26, 2015 ... the "2016 Future Horizons and Growth ... Testing Market: Supplier Shares, Country Segment Forecasts, ... their offering. --> ) ... "2016 Future Horizons and Growth Strategies in ...
(Date:11/26/2015)... Nov. 26, 2015 Research and Markets ( ... "Advanced Wound Care Market by Type (Dressings, Therapy Devices, ... (In-Patient Facility, Out-Patient Facility), and Geography - Global Forecast ... --> --> The purpose ... and forecast of the global advanced wound care market. ...
Breaking Medicine Technology: