Targeting the FLICE Inhibitory Protein (FLIP) in cancer therapy.

In some cases, treatment of ovarian cancer cells with tumor necrosis factor-alpha can induce an apoptotic signal leading to the death of these cells; however, many ovarian malignancies are resistant to the effects of TNF-alpha. A new publication describes how these ovarian tumors may evade death receptor-mediated apoptosis. Apparently, the extracellular signals transduced by death receptors (e.g., TNF receptors) are extinguished before the cascade of caspases, which proteolytically cleave other proteins, can be activated. Overexpression of FLIP, a protein that blocks the caspase activity of FLICE, mediates the observed resistance. Thus, FLIP, which normally prevents inappropriate apoptosis, may become a tumor progression factor. Strategies to overcome this FLIP-mediated blockade of programmed cell death in tumors might become useful for positive prognoses.