Mechanism Boosts Effects of Cancer Treatments

Scientists have found a new mechanism of pathway activation known to be involved in many cancers. In addition, they discovered that when this mechanism is blocked, cells may become more sensitive to chemotherapeutic agents and radiation, thereby making them easier to kill.

Researchers from Mount Sinai School of Medicine (New York, NY, USA) studied the Wnt pathway, which is known to be essential to regulation of cell differentiation. Once differentiated, cell proliferation is restricted. When triggered, the Wnt pathway instructs cells not to differentiate, allowing them to grow uncontrollably, which can then lead to tumor development.

The Mount Sinai investigators found that in some ovarian, breast, and colon cancer cells this pathway becomes activated by the triggering of a receptor on the surface of the cell. The cell can stimulate itself, remain in an undifferentiated condition, and continue to grow unchecked. Also, they found that the pathway can be inactivated at the cell surface by compounds that block the receptor. When inactivated, these cancer cells become more sensitive to agents that induce cell death.

Whereas it has been known that the Wnt pathway is involved in nearly all cases of colon cancer and in some ovarian and skin cancers, this research was the first to implicate this pathway in breast cancer and to identify this mechanism in human tumor cells. The study was published in the November 2004 issue of Cancer Cell.

"An increasing number of cancer therapeutic agents are being developed to block pathways activated by interactions at the cell surface. This research provides a novel target to interfere with a pathway that is implicated in many cancer types,” remarked Dr. Stuart Aaronson, professor and chairman of oncologic sciences at Mount Sinai School of Medicine.

Dr. Anna Bafico, assistant professor of oncologic sciences at Mount Sinai concluded, "Selectively interfering in this pathway in cancer cells with this mechanism may make them more sensitive to existing treatments.”