The role of cellular flice inhibitory protein (c-FLIP) in the pathogenesis and treatment of cancer

Protection from death receptor (DR)-mediated apoptosis has been proposed as an important step in the development of malignancy, enabling tumour cells not only to survive and escape antitumour immune responses, but also to develop resistance to chemotherapy or other cancer treatments. An important regulator of DR-induced death is the cellular FADD-like IL-1 beta-converting enzyme inhibitory protein (c-FLIP) which, when overexpressed, can protect tumour cells from apoptosis. This review focuses on the role of c-FLIP as a tumour progression factor, with particular emphasis on recent work from the authors' laboratory concerning the contribution of c-FLIP to the pathogenesis of Hodgkin's lymphoma. The possibility of targeting c-FLIP as an approach to the treatment of cancer and, in particular, Hodgkin's lymphoma is discussed.