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

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