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-1beta-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.
Dutton
Amanda
A
Cancer Research UK Institute for Cancer Studies, Division of Cancer Studies, Department of Pathology, The Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Young
Lawrence S
LS
Murray
Paul G
PG
D000818:Animals; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D018450:Disease Progression; D016503:Drug Delivery Systems / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D006689:Hodgkin Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins