Targeting cellular FLICE-like inhibitory protein as a novel approach to the treatment of Hodgkin's lymphoma.

Abstract

Hodgkin's lymphoma is one of the most common lymphoid cancers, particularly among young adults. Although there have been dramatic improvements in the treatment of Hodgkin's lymphoma, leading to high cure rates in some groups, current combination chemotherapy regimes are associated with significant secondary complications in long-term survivors. Furthermore, although a proportion of patients with Hodgkin's lymphoma will be cured, there still remains a significant rate of relapse and also a smaller proportion of poor responders who will go on to die of their disease. Therefore, developments in the treatment of Hodgkin's lymphoma must be directed at improving cure rates and reducing the burden of secondary complications. In recent years, the underlying pathogenesis of Hodgkin's lymphoma has become better understood. In particular, it is emerging that a key pathogenic event in Hodgkin's lymphoma is protection from Fas-induced cell death. Recent studies by the authors' group, and others, have demonstrated that this is, in part, due to the expression by Hodgkin/Reed-Sternberg cells of the cellular Fas-associated death domain-like IL-1 converting enzyme (FLICE)-like inhibitory protein molecule, a potent inhibitor of Fas-induced death. In this review, the role of cellular FLICE-like inhibitory protein in the pathogenesis of Hodgkin's lymphoma will be explored and also the possibility of targeting this molecule in order to provide an alternative and potentially safe approach to the treatment of Hodgkin's lymphoma will be investigated.