Jahangiri Sudy, Friedberg Jonathan, Barr Paul
University of Rochester Medical Center , Rochester, NY , USA
Expert Opin Emerg Drugs. 2014 Sep;19(3):367-83. doi: 10.1517/14728214.2014.929663. Epub 2014 Jun 24.
non-Hodgkin's lymphoma (NHL) accounts for 4.3% of all new cancers in the United States. Even in its most curable subtypes, approximately 30% of patients succumb to their disease. For these patients there is clear need for more effective therapy. In indolent NHL where survival is prolonged, the aim of therapy is improving quality of life and limiting the burden of therapy.
The key signaling mechanisms of normal B-cells, the changes that are seen in signaling in NHL, and the targets of novel protein kinase inhibitors (PKIs) are discussed. The efficacy of these agents in both aggressive and indolent histologies is reviewed. Logical combinations of novel and traditional agents are explored. Ongoing studies of the new agents are discussed.
PKIs will likely modify standard therapeutic paradigms in NHL. As use of these agents increases and combination studies continue, optimal use will depend on individual disease characteristics, goals of therapy as well as patient and societal costs. Future clinical trials need to be designed with appropriate end points given prolonged use in many cases of these orally administered, well tolerated compounds. Further, safeguards against cumulative and/or unique side effects need to be in place given the novel signaling pathways being targeted.
非霍奇金淋巴瘤（NHL）占美国所有新发癌症的4.3%。即使在其最可治愈的亚型中，仍有大约30%的患者死于该疾病。对于这些患者，显然需要更有效的治疗方法。在生存期延长的惰性NHL中，治疗的目标是提高生活质量并减轻治疗负担。
讨论了正常B细胞的关键信号传导机制、NHL信号传导中出现的变化以及新型蛋白激酶抑制剂（PKI）的靶点。综述了这些药物在侵袭性和惰性组织学中的疗效。探索了新型药物与传统药物的合理联合使用。讨论了新型药物正在进行的研究。
PKI可能会改变NHL的标准治疗模式。随着这些药物的使用增加以及联合研究的继续，最佳使用将取决于个体疾病特征、治疗目标以及患者和社会成本。鉴于这些口服、耐受性良好的化合物在许多情况下会长期使用，未来的临床试验需要设计适当的终点。此外，鉴于所靶向的新型信号通路，需要采取措施防范累积和/或独特的副作用。
