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Experimental drug kills breast cancer stem cells

* Treatment showed promise in human tumors

* Drug hits cancer stem cells

* Could make chemotherapy more effective

CHICAGO, Dec 11 (Reuters) - An experimental drug was effective at killing breast cancer stem cells -- a kind of master cancer cell that resists chemotherapy, U.S. researchers said on Friday.

Studies in animals and women with advanced breast cancer showed the experimental compound MK-0752, under development by Merck & Co Inc MRK.N, was able to kill off cancer stem cells that linger in the breast after chemotherapy.

Researchers are still trying to understand the role cancer stem cells play in promoting different types of cancer, but many teams think they may explain why so many cancers come back even after treatment with powerful chemotherapy and radiation.

“These cells are different from the tumor. They are resistant to therapy. They regrow. They cause relapse and metastases,” said Dr. Jenny Chang of Baylor College of Medicine, who presented her findings at the American Association for Cancer Research San Antonio Breast Cancer Symposium.

A team at the Massachusetts Institute of Technology and the Broad Institute in August reported a similar finding in breast cancer cells and in mice in the journal Cell.

In the latest study, supported by funding from Merck, Chang and colleagues injected mice with breast cancer cells taken from patients and grew human tumors in the mice that were identical to those growing in women.

The team then studied the specific properties of the cancer stem cells, and focused on the Notch pathway, which is important for normal development of breast tissue.

“We found this was also active in cancer stem cells,” Chang said in a telephone interview.


Chang said breast cancer stem cells were dependent on the Notch pathway for survival. Merck’s drug MK-0752, a compound called a gamma-secretase inhibitor, blocks that pathway.

When the team combined the drug with regular chemotherapy in mice, “we found we managed to hit cancer stem cells,” Chang said.

The compound also is working in a study involving 35 women with advanced breast cancer. Breast cancer biopsies before and after treatment show it reduces the number of breast cancer stem cells.

“We do see responses. After a period of time, the tumors regress, but more importantly, we are attacking the cancer stem cell component,” Chang said.

She said the next step was to test the drug combination in large, late-stage trials.

“I think this is very encouraging data,” said Dr. Max Wicha of the University of Michigan, who worked on the study.

“We know it can be given safely with very little if any extra side effects. We know that it knocks down the stem cells. The next logical step is to see if it really benefits patients,” he said. (Editing by Peter Cooney)