Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, No.324, Jingwu Road, Jinan, Shandong 250021, China.
Shandong University School of Medicine, Jinan, Shandong 250012, China.
Anticancer Agents Med Chem. 2019;19(17):2047-2059. doi: 10.2174/1871520619666190925143216.
Diffuse Large B Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma which is heterogeneous both clinically and morphologically. Over the past decades, significant advances have been made in the understanding of the molecular genesis, leading to the identification of multiple pathways and molecules that can be targeted for clinical benefit.
The current review aims to present a brief overview of signal pathways of DLBCL, which mainly focus on B-cell antigen Receptor (BCR), Nuclear Factor-κB (NF-κB), Phosphatidylinositol-3-Kinase (PI3K) - protein kinase B (Akt) - mammalian Target of Rapamycin (mTOR), Janus Kinase (JAK) - Signal Transducer and Activator (STAT), Wnt/β-catenin, and P53 pathways.
Activation of signal pathways may contribute to the generation, development, chemotherapy sensitivity of DLBCL, and expression of pathway molecules is associated with the prognosis of DLBCL. Some agents targeting these pathways have been proved effective and relevant clinical trials are in progress. These agents used single or combined with chemotherapy/each other might raise the possibility of improving clinical outcomes in DLBCL.
This review presents several signal pathways of DLBCL and targeted agents had a tendency to improve the curative effect, especially in high-risk or relapsed/refractory DLBCL.
弥漫性大 B 细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤,在临床上和形态上均具有异质性。在过去的几十年中,人们对其分子发生机制的理解取得了重大进展,从而确定了多种可用于临床获益的途径和分子。
本综述旨在简要概述 DLBCL 的信号通路,主要集中在 B 细胞抗原受体(BCR)、核因子-κB(NF-κB)、磷脂酰肌醇 3-激酶(PI3K)-蛋白激酶 B(Akt)-哺乳动物雷帕霉素靶蛋白(mTOR)、Janus 激酶(JAK)-信号转导和转录激活因子(STAT)、Wnt/β-catenin 和 P53 通路。
信号通路的激活可能有助于 DLBCL 的发生、发展和化疗敏感性,并且通路分子的表达与 DLBCL 的预后相关。一些针对这些通路的药物已被证明有效,相关临床试验正在进行中。这些药物单独或联合化疗/彼此联合使用可能有改善 DLBCL 临床结局的可能性。
本综述介绍了几种 DLBCL 的信号通路,靶向药物有改善疗效的趋势,特别是在高危或复发/难治性 DLBCL 中。