Drug compound leads to death of ovarian cancer cells resistant to chemotherapy

April 17, 2008

In a discovery that may be useful for maintaining remission in chemo-resistant ovarian cancer, Yale scientists report that pre-clinical studies have shown the drug compound NV-128 can induce the death of ovarian cancer cells by halting the activation of a protein pathway called mTOR.

Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine, and associate research scientist Ayesha Alvero, M.D. presented the data April 15 during an oral presentation at the annual meeting of the American Association for Cancer Research.

In cancer cells, mTOR signals enhance tumor growth and may be associated with resistance to conventional therapies. Inhibition of mTOR could shut down many of these survival pathways, including proteins that protect the mitochondria of cancer cells.

NV-128, developed by Novogen Limited, holds promise as a more targeted therapy for ovarian cancer because it works differently from traditional therapies that are dependent on enzymes known as caspases to trigger cell death. Therapies using caspases to kill cancer cells can be ineffective in chemo-resistant cancer cells due to mutations that short-circuit signals that trigger cancer cell death.

"We consider that the capacity of NV-128 to trigger caspase-independent cell death, in otherwise chemoresistant ovarian cancer cells, opens new possibilities for the use of NV-128 as a potential addition to conventional chemotherapy targeting ovarian cancer cells," said Mor.

In the context of developing therapies for late stage ovarian cancer, Mor said, the finding may be "a key step to the development of alternative targeted therapy for patients with cancer recurrence."
-end-


Yale University

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