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New Drug May Prevent Recurrence, Improve Survival in Ovarian Cancer

Synergistic Effects Seen When Combined With Cisplatin in Mice

New research  in mice has identified a compound that prevents ovarian cancer recurrence by eradicating the cancer stem-like cells that conventional chemotherapy leaves behind. The compound, known as 673A, is a potent inhibitor of the ALDHA pathway that cancer cells rely on to get rid of the toxins that they produce when they replicate quickly.

A team of scientists led by Dr. Ronald Buckanovich, a professor of medicine at the University of Pittsburgh in Pennsylvania, discovered that 673A targets stem-like ovarian cancer cells and stops the cancer from returning. Dr. Buckanovich explains that even though chemotherapy can destroy up to 99 percent of ovarian cancer cells, the traditional treatment still "misses" stem-like cancer cells.

The scientists found that, as a single agent, 673A had only a slight effect on these cells, but that it was highly effective when used in combination with the chemo drug cisplatin. The researchers also treated chemoresistant cancer cells with 673A, injected them into mice, and monitored the growth of the tumor for 28 days. Although the cisplatin-treated cells produced tumors similar in size to those produced by untreated cells, 673A-treated cells produced tumors that were 4–5-fold smaller.

Dr. Buckanovich and his team then injected chemoresistant ovarian cancer cells into rodents. They treated one group of mice with chemo alone and another group with chemo plus 673A. The researchers monitored the mice for 6 months. When 673A was used in combination with chemotherapy, the tumors in almost two-thirds of the mice were in remission after 6 months. By contrast, all of the rodents that received only chemo died. Dr. Buckanovich stated that, in conjunction with chemotherapy, 673A was 10 times more effective at destroying stem-like cells than previous inhibitors of the same type.

According to the National Cancer Institute, there were over 22,000 new cases of ovarian cancer in the United States in 2018; more than 14,000 of these resulted in death. Just under 50 percent of those who develop ovarian cancer go on to survive for 5 years.

Ovarian cancer is not very common, but its recurrence rate is notoriously high. According to previous estimates, "between 70 and 90 percent of all women with ovarian cancer" will have a recurrence at some point after their diagnosis.

The researchers caution that the drug needs more work before it can be approved for human use. The drug is not yet as soluble as it should be, and it doesn't last very long in the body.

Dr. Buckanovich and his colleagues published their findings in the journal Cell Reports.

Source: Medical News Today, March 14, 2019

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