Overcoming resistance to trail-induced apoptosis in prostate cancer by regulation of c-FLIP.

Using Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL) for cancer therapy is attractive, because TRAIL is effective against cancer cells without inducing significant cytotoxicity, making it an ideal cancer drug. However, some cancer cells evade TRAIL-induced apoptosis and become resistant. We have been investigating the molecular mechanisms that differentiate between TRAIL-resistant and TRAIL-sensitive prostate cancer cells. We have found that transcriptional regulation of the anti-apoptotic molecule, c-FLIP(L), can regulate sensitivity of cancer cells to TRAIL. We have found that c-Fos, represses expression of c-FLIP(L), and promotes TRAIL-induced apoptosis. Identifying molecular mechanisms that differentiate between sensitive and resistant cancer cells will help improve pro-apoptotic cancer therapies.