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Hereditary ovarian cancer: Beyond the usual suspects. February 13, 2012

Posted by patoconnor in cancer, gynecological cancer, ovarian cancer, tubal cancer, Uncategorized, uterine cancer, vaginal cancer.
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Hereditary ovarian cancer: Beyond the usual suspects.

Feb 2012

Pennington KPSwisher EM.

Abstract

In the past, hereditary ovarian carcinoma was attributed almost entirely to mutations in BRCA1 and BRCA2, with a much smaller contribution from mutations in DNA mismatch repair genes. Recently, three new ovarian cancer susceptibility genes have been identified: RAD51C, RAD51D, and BRIP1. In addition, germline mutations in women with ovarian carcinoma have been recently identified in many of the previously identified breast cancer genes in the Fanconi anemia (FA)-BRCA pathway. While mutations in genes other than BRCA1 and BRCA2 are each individually rare, together they make up a significant proportion of cases. With at least 16 genes implicated in hereditary ovarian cancer to date, comprehensive testing forovarian cancer risk will require assessment of many genes. As the cost of genomic sequencing continues to fall, the practice of evaluating cancer susceptibility one gene at a time is rapidly becoming obsolete. New advances in genomic technologies will likely accelerate the discovery of additional cancer susceptibility genes and increase the feasibility of comprehensive evaluation of multiple genes simultaneously at low cost. Improved recognition of inherited risk will identify individuals who are candidates for targeted prevention. In addition, identifying inherited mutations in a variety of FA-BRCA pathway genes may aid in identifying individuals who will selectively benefit from PARP inhibitors.

Science Direct

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New Treatment for Ovarian Cancer Shows Promise November 20, 2008

Posted by patoconnor in cancer, gynecological cancer, ovarian cancer, tubal cancer, uterine cancer, vaginal cancer.
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Ovarian Cancer Cells Are Killed By Platinum-Phosphate Compounds

A new class of compounds called phosphaplatins can effectively kill ovarian, testicular, head and neck cancer cells with potentially less toxicity than conventional drugs, according to a new study published this week in the journal Proceedings of the National Academy of Sciences.

The compounds could be less harmful than current cancer treatments on the market such as cisplatin and carboplatin because they don’t penetrate the cell nucleus and attach to DNA, said lead author Rathindra Bose. Conventional drugs can interfere with the functions of the cell’s enzymes, which lead to side effects such as hearing and hair loss and kidney dysfunction.

Though scientists don’t fully understand the mechanism by which the phosphaplatins kill cancer cells, they suspect that the compounds bind to the cell surface membrane proteins and transmit a “death signal” to the interior of the cell, Bose said. The compounds are created by attaching platinum to a phosphate ligand, which can readily anchor to the cell membrane. Future studies will focus on identifying the exact process.

“The findings suggest a paradigm shift in potential molecular targets for platinum anticancer drugs and in their strategic development,” said Bose, a professor of biomedical sciences and chemistry and vice president for research at Ohio University who conducted the work while at Northern Illinois University.

The first drug developed for the treatment of ovarian and testicular cancers, cisplatin, was approved for use in 1982. Though it’s 95 percent effective, it works best during the early stages of the disease, and some patients develop a resistance to it. Two drugs introduced later, carboplatin and oxaliplatin (which is used for colorectal cancer), overcame some of those problems, but their potency can harm the immune system of patients, said Bose, who has been studying alternative compounds and targets for these cancers for 25 years.

Phosphaplatins have the potential to be more efficient, more targeted and create fewer side effects in the patient, Bose said. The new study shows that the phosphaplatins can kill ovarian cells at half of the dosage of conventional drugs, but are just as potent. Unlike cisplatin, which can decompose quickly and create additional toxic side effects through the decomposition products, the new compounds show no signs of degradation after seven days, he added.

A U.S. patent is pending on the work; two provisional patents have been filed. Bose and his colleagues next will test the compounds in mice models.

Co-authors of the study are Leila Maurmann of Kansas State University, and Robert Mishur, Linda Yasui, Shefalika Gupta, W. Scott Grayburn, Heike Hofstetter and Tara Milton, all of Northern Illinois University.

By: Ohio University – Wed, 11/19/2008 – 16:16