Chemo-resistant Ovarian Cancer Cells can be Destroyed, Yale Researchers Report

Yale School of Medicine researchers today released laboratory based data identifying significant new signaling pathways for ovarian cancer and have found that drugs can be used to successfully alter signals to induce cancer cell death.

The results were presented at the Society for Gynecologic Investigation 50th Annual Meeting in Washington, D.C.

Researchers, led by associate professors Gil Mor, M.D., and Thomas Rutherford, M.D., in the Department of Obstetrics and Gynecology at Yale School of Medicine, used the experimental anti-cancer agent that caused chemo-resistant cancer cells to die. They also presented data indicating two signaling pathways that regulate cancer cells. They found that the drug, phenoxodiol, works by altering the signals made by these pathways.

“We’ve found that this drug is an efficient inducer of cell death in ovarian cancer cells and sensitizes the cancer cells to Fas-mediated apoptosis (cell death),” said Mor. “These findings demonstrate a novel non-toxic drug that controls FLIP/XIAP function and has the potential to eliminate tumor cells through Fas-mediated apoptosis.”

A multi-center phase II trial is underway to investigate the drug phenoxodiol in women with chemo-resistant ovarian cancer. The trial is being conducted at Yale University School of Medicine, the only participating U.S. site.

“In the laboratory, we have identified phenoxodiol to be an extremely effective agent in causing ovarian cancer cells to undergo cell death,” said Rutherford. Clinically, we are investigating possible toxicity and response at different dose levels in women with chemo-resistant ovarian cancer. In some of these women, disease regression or stabilization has been realized.”

Dr. Graham Kelly, director of phenoxodiol research at Marshall Edwards Inc., added, “What’s important here is not just the discovery that phenoxodiol causes chemo-resistant ovarian cancer cells to die, but also that they know how it makes that happen - by altering the messages sent by two signaling pathways that otherwise fail to tell these cells to self-destruct.”

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Karen N. Peart: karen.peart@yale.edu, 203-432-1326