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North Shore-LIJ Team Links miRNA Pattern to Ovarian Cancer Survival, Plans Validation Work

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By Doug Macron

A team of researchers this week reported on the discovery of a microRNA expression pattern that, in a preliminary study, was able to identify ovarian cancer patients who would survive the disease with appropriate treatment.

According to one of the investigators, the findings suggest that the signature could not only be used to inform a patient of her likelihood of survival, but also point to miRNAs that could be used as an adjuvant to boost the efficacy of existing treatments.

In the first case, “if a woman who has ovarian cancer goes and has a blood test [before surgery] that [shows] the survival pattern, all her worries and negative emotions are removed, regardless of [the disease's] stage,” Iuliana Shapira, director of cancer genetics at North Shore-Long Island Jewish Health System's Monter Cancer Center, told Gene Silencing News.

For those who don't express the miRNA survival pattern, it may be possible to develop a treatment based on mimics of the miRNAs that comprise the survival pattern, she added.

Results from the study were presented at the American Association for Cancer Research annual meeting in Chicago this week, and included data showing significantly increased expression of a number of miRNAs in response to chemotherapy.

Shapira said that she and her colleagues began collecting plasma samples in 2004 from patients undergoing surgical removal of ovarian masses. She noted that surgery is the standard of care since there is no test for determining whether such masses are malignant and biopsy is not an option because it can cause a tumor to spread.

According to the poster presented at AACR, plasma was obtained from patients before and after surgery; during and after chemotherapy; and at ovarian cancer relapse.

The team examined samples from 50 cancer patients, six patients with benign masses, and 10 normal controls.

Among the cancer cohort, two were deemed cured of their disease, showing no evidence of ovarian cancer five years after surgery and chemotherapy. Twenty-two patients died within 36 months of surgery and after receiving at least three lines of chemotherapy, while 11 patients were found to be cancer-free with treatment 16 months after surgery. A total of four patients remained alive more than 37 months after surgery and continued to receive chemotherapy.

Three patients died of unrelated causes including surgical complications, according to the poster, and eight patients received treatment too soon to determine their outcomes.

Shapira said this week that the number of cured patients has increased to six since the time the poster was prepared.

The investigators found that all of the cured patients expressed the miRNA signature that indicated survival. Another 18 patients who remain alive have also shown this expression pattern, but Shapira cautioned that they have not yet reached the five-year mark that indicates cured disease.

The normal controls, patients with benign masses, and those who died from the cancer did not show the miRNA signature.

Specific details about the survival pattern were not provided, but Shapira said that “the statistics are excellent.

“The correlation is more than 90 percent,” she added. “Compared to normal [samples], these are expressed [at] hundreds of fold” greater levels, regardless of disease stage.

She also said that the findings are being prepared for publication, at which point more information will be provided, but cautioned that the data are very preliminary and must be validated in additional samples.

To that end, Shapira and her team have applied for a National Institutes of Health grant to study the miRNA signature in an additional 100 samples from ovarian cancer patients. Should the results of that work prove positive, she hopes to find an industry partner interested in developing a test to determine a patient's chances of surviving ovarian cancer.

Additionally, she aims to find a company that could help develop a drug based on the miRNAs that could increase the efficacy of treatment in patients who do not naturally express the survival pattern.

Also through their study, Shapira and her colleagues found that the expression of a number of miRNAs sharply increases in ovarian cancer patients receiving chemotherapy compared with pre-surgical levels. Most notable were miR-16, which was over-expressed 80-fold, and miR-195, which increased 50-fold.

“We conclude that chemotherapy changes the plasma [miRNAs, which] … may have long-term effects as evidenced by the long-term effects chemotherapy has on some patients,” the researchers wrote in the AACR poster.

“It is not unusual for heavily treated patients to develop myelodysplastic syndrome and acute leukemia when they received either platinum or other agents for ovarian cancers,” they noted. However, “the contribution of [miRNA] changes to the development of secondary malignancies in cancer patients is not yet clear.”


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