Aspirin derivative may treat recurrence of ovarian cancer

Women who are successfully treated for ovarian cancer often have a relapse of the disease, which becomes resistant to the cisplatin chemotherapy that worked before.

Now, researchers have discovered that the new drug NCX-4016, an aspirin derivative, re-sensitizes ovarian cancer cells to chemotherapy with cisplatin and kills ovarian cancer cells.

Although this work has only been done in ovarian cancer cells in the laboratory, the hope is that one day this treatment will defeat recurrent ovarian cancer. The finding appears in this week's edition of the Proceedings of the National Academy of Sciences.

"Ovarian cancer is usually diagnosed very late," says lead researcher Periannan Kuppusamy, a professor of internal medicine and biomedical engineering at the Dorothy M. Davis Heart and Lung Research Institute at Ohio State University. "After that, there are not many treatments available -- usually surgery to remove the tumor, then treatment with cisplatin."

Within six to 12 months after treatment, however, the cancer often returns, Kuppusamy says. "When this happens, you cannot give cisplatin. This time the drug will not work," he notes. "Since it was treated with cisplatin before, it will develop some kind of resistance to the drug."

In experiments with ovarian cancer cells, Kuppusamy's team has found that NCX-4016 releases nitric oxide, which in turn re-sensitizes the tumor to cisplatin. "Now, cisplatin at the same usual dose can be used to kill tumor cells," Kuppusamy says. "The drug also works to kill the cancer cells."

In women with recurrent ovarian cancer, the combination of NCX-4016 and cisplatin will be more effective in treating these drug-resistant cancer cells, Kuppusamy says.

"The next step is to use this drug combination in animals," Kuppusamy says. "The third step is clinical trials. One day patients can be treated using this drug. The drug is a modification of aspirin, so there may be no toxicity."

One expert thinks that before this drug can be used in people, it needs to be tested to be sure it has no toxic side effects, especially to other body systems. "This study does not show what happens to other compounds in cells," says S.K. Dey, director of the division of reproductive and developmental biology at Vanderbilt University Medical Center.

Dey believes that using the drug, combined with cisplatin, seems promising for treating ovarian cancer. "However, we have been fooled in the past by relying only on cell cultures. In culture, many things happen that don't happen in vivo," he adds.

Dey also cautions that a drug that releases nitric oxide can have other effects on body systems. "Like cardiovascular effects," he says.

Another expert thinks human trials need to be done as quickly as possible.

"This novel agent, NCX-4016, is now shown in the cell line experiments in this paper to have both intrinsic anti-tumor activity, as well as platinum-modulation activity," says Dr.

Robert Morgan Jr., section head of medical gynecologic oncology at City of Hope Cancer Center in Duarte, Calif. "Furthermore, it appears to be quite nontoxic to patients."

Given its safety and the now-proven ability to help in treating ovarian cancer, at least in a lab setting, Morgan wants to see it moved to human trials. "It is important that the hypotheses generated by these experiments be tested in a clinical trial of platinum-resistant ovarian cancer patients as soon as possible to verify if there will be clinical utility in this approach," he says.

Ovarian cancer is the eighth most common cancer -- not including skin cancer -- in women, and the fifth-leading cause of cancer death. The American Cancer Society estimates that there will be about 20,180 new cases of ovarian cancer in 2006, and that about 15,300 women will die of the disease.

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c.2006 HealthDay News