( A recent study finds that TACE inhibit...)A New Strategy to Control Breast Cancer,Health

A recent study finds that, TACE inhibitors currently developed for treating rheumatoid arthritis can also be employed to control proliferation of tumor cells. TACE is// strongly present in a form of breast cancer, which responds poorly to current therapies.

TACE (tumor necrosis factor-alpha-converting enzyme) acts like a “molecular scissors” that releases a pair of ligands, called Amphiregulin and TGF-alpha, from the cell surface. These ligands activate EGFR.

EGFR, which stands for Epidermal Growth Factor Receptor, is the protein on the outer surface of a cell that is activated by EGF and related growth factors and signals for the cell to divide. Given that one of the hallmarks of cancer is cell division run amok, the reduction of high levels of EGFR activity has long been a primary target for anti-cancer drug development. So far, however, drugs aimed at directly inhibiting EGFR activity have met with only limited success in the cancer clinic, primarily in a small number of lung cancers.

Bissell and Kenny, researchers with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have demonstrated that by targeting TACE (also known as ADAM17) with either molecular inhibitors or short interfering RNAs (siRNAs) that silence the TACE gene, the shedding of Amphiregulin and TGF-alpha ligands could effectively be blocked.

This also resulted in the inhibition of EGFR signaling and the reversion of malignant characteristics in tumor cells. It is the first reported use of protease inhibitors to stop breast cancer cell proliferation and restore the normal breast tissue structure.

Tumor cells, says Bissell, exist in the same microenvironment as healthy cells and must therefore appropriate normal physiological processes to facilitate their growth and spread. This idea can open up potential new avenues and targets for diagnostic and therapeutic applications.

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