New mechanism that contributes to the development of some breast and ovarian cancers

Nov 23 2004

Researchers at Mount Sinai School of Medicine have discovered a new mechanism of activation of a pathway known to be implicated in many cancers.

Additionally, the researchers found that when this mechanism is blocked cells may become more sensitive to radiation and chemotherapeutic agents, thus making them easier to destroy. The research was published in the November issue of Cancer Cell.

The researchers investigated the Wnt pathway, which is known to be integral to regulation of cell differentiation – the process by which a stem cell develops into a specific type of cell. Once differentiated, cell proliferation is limited. When activated the Wnt pathway tells cells not to differentiate allowing them to grow unchecked, which can lead to development of a cancer.

Drs. Anna Bafico, Stuart Aaronson and colleagues at Mount Sinai School of Medicine discovered that in some breast, ovarian and colon cancer cells this pathway becomes active through triggering of a receptor on the surface of the cell. So, the cell can stimulate itself, remain in an undifferentiated state and continue to proliferate. Furthermore, they discovered that the pathway can be shut off at the cell surface by compounds that block the receptor. Once turned off, such cancer cells become more sensitive to agents that induce cell death.

While it was previously known that the Wnt pathway is involved in almost all cases of colon cancer and in some ovarian, and skin cancers, this study was the first to implicate this pathway in breast cancer and to identify this mechanism in human tumor cells.

"An increasing number of cancer therapeutic agents are being developed to block pathways activated by interactions at the cell surface," said Dr. Aaronson, Professor and Chairman of Oncological Sciences at Mount Sinai School of Medicine. "This research provides a novel target to interfere with a pathway that is implicated in many cancer types."

"Selectively interfering in this pathway in cancer cells with this mechanism may make them more sensitive to existing treatments," said Dr. Bafico, Assistant Professor of Oncological Sciences at Mount Sinai School of Medicine.