Dutton Amanda, Burns Alan T H, Young Lawrence S, Murray Paul G
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK.
Expert Rev Anticancer Ther. 2006 Jun;6(6):911-9. doi: 10.1586/14737140.6.6.911.
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.
霍奇金淋巴瘤是最常见的淋巴系统癌症之一，在年轻成年人中尤为常见。尽管霍奇金淋巴瘤的治疗已经取得了显著进展，使得某些群体的治愈率很高，但目前的联合化疗方案在长期存活者中会引发严重的继发性并发症。此外，虽然一部分霍奇金淋巴瘤患者能够治愈，但仍有相当比例的患者会复发，还有一小部分反应不佳的患者会最终死于该疾病。因此，霍奇金淋巴瘤治疗的发展必须致力于提高治愈率并减轻继发性并发症的负担。近年来，霍奇金淋巴瘤的潜在发病机制已得到更好的理解。特别是，越来越明显的是，霍奇金淋巴瘤中的一个关键致病事件是免受Fas诱导的细胞死亡。作者团队及其他团队最近的研究表明，这部分是由于霍奇金/里德-斯腾伯格细胞表达了细胞Fas相关死亡结构域样白细胞介素-1转换酶（FLICE）样抑制蛋白分子，这是一种Fas诱导死亡的强效抑制剂。在这篇综述中，将探讨细胞FLICE样抑制蛋白在霍奇金淋巴瘤发病机制中的作用，同时也将研究靶向该分子以提供一种替代的、潜在安全的霍奇金淋巴瘤治疗方法的可能性。
