Disrupting two cell mechanisms in combination can suppress aggressive breast cancer in mice

NEW YORK, September 29, 2003 Scientists at Memorial Sloan-Kettering Cancer Center and colleagues found that by inhibiting both the proteins responsible for breast cancer growth and those required for the formation of new blood vessels, they could more effectively suppress the growth of extremely aggressive breast tumors in mice. In a surprising finding, the researchers showed that mice harboring a mutation commonly found in human breast cancers developed tumors that were able to grow despite a defect in angiogenesis or new blood vessel formation. However, when these mice were also treated with a chemotherapy drug under development at Memorial Sloan-Kettering that inhibits Hsp90 (a cell survival protein), the chemotherapy was significantly more effective in the mice with abnormal angiogenesis so that tumor growth was completely suppressed. These findings, published in the October 3 issue of the Proceedings of the National Academy of Science, suggest that combining agents that target these two cellular functions should be evaluated for the treatment of advanced breast cancer.

"It was unexpected that the tumors would be able to overcome an inhibition to angiogenesis," said Paola de Candia, Ph.D., a researcher in the Benezra laboratory and first author of the study. "The mice developed large tumors despite the impairment in their ability to form new blood vessels caused by Id deficiency. The tumors were morphologically different with cystic (liquid) centers and a narrow rim of tumor cells. The cells in the rim continued to proliferate and invade tissue. Ultimately, they metastasized, suggesting that inhibiting tumor angiogenesis was not sufficient to suppress tumor growth and progression."

In earlier research, the study's senior author, Dr. Robert Benezra, and colleagues had shown that mice with two of their four Id proteins genetically altered or "knocked out" had impaired angiogenesis which resulted in an inability to grow capillaries from existi

Contact: Joanne Nicholas
Memorial Sloan-Kettering Cancer Center

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