摘要
慢性淋巴细胞白血病的发病机制在近百年已有了重大意义的进展,这使得它的治疗方式一下有了很多选择。BCR信号发射抑制剂,如ibrutinib 和idelalisib和促凋亡剂(如ABT-199,它在最初临床试验中展现很好的前景并且一直在最近的发展前沿)。然而,除了那些令人激动的早期数据,这些制剂并不会治愈CLL,并且其耐药机制已得到证实。根据这些考虑,我们需要能替代的治疗方法。来那度胺,酞醚哌啶酮的二代衍生物,在CLL治疗中表现出了良好的临床活性。它通过在CLL微环境中调节降低CLL细胞增殖,提高抗肿瘤免疫反应,减少促肿瘤因子起作用。这篇综述讨论了我们对来那度胺在健康细胞和CLL中行为机制的现下理解。也总结了已发表的关于这个药物的临床试验,并提出了这个药物在CLL中的当下作用。
关键词: 慢性淋巴细胞白血病,免疫抑制,T细胞,自然杀伤细胞,CD40配体,来那度胺,癌症疫苗,异基因造血干细胞移植
Current Cancer Drug Targets
Title:Mechanistic and Clinical Aspects of Lenalidomide Treatment for Chronic Lymphocytic Leukemia
Volume: 16 Issue: 8
Author(s): John C. Riches and John G. Gribben
Affiliation:
关键词: 慢性淋巴细胞白血病,免疫抑制,T细胞,自然杀伤细胞,CD40配体,来那度胺,癌症疫苗,异基因造血干细胞移植
摘要: There have been significant advances in our understanding of the pathogenesis of chronic lymphocytic leukemia (CLL) over the last decade, which has been accompanied by a rapid increase in treatment options. Inhibitors of BCRsignaling such as ibrutinib and idelalisib, and pro-apoptotic agents such as ABT- 199 have shown great promise in initial clinical trials and have been at the forefront of recent developments. However, despite the encouraging early data, these agents do not appear to represent a “cure” for CLL and mechanisms of resistance to these agents have already been identified. In light of these considerations there remains a need for alternative treatment strategies. Lenalidomide, a second-generation derivative of thalidomide, has been demonstrated to have significant clinical activity in CLL. Its effect appears to be mediated by reduction of CLL-cell proliferation, improvement of anti-tumor immune responses and reduction of pro-tumoral factors in the CLL microenvironment. This review discusses our current understanding of the mechanism of action of lenalidomide on both healthy cells and in CLL. It also summarises the published clinical trial experience with this drug, and proposes an ongoing role for this agent in the CLL armamentarium.
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Cite this article as:
John C. Riches and John G. Gribben , Mechanistic and Clinical Aspects of Lenalidomide Treatment for Chronic Lymphocytic Leukemia, Current Cancer Drug Targets 2016; 16 (8) . https://dx.doi.org/10.2174/1568009616666160408145741
DOI https://dx.doi.org/10.2174/1568009616666160408145741 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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