Miao Yi, Medeiros L Jeffrey, Xu-Monette Zijun Y, Li Jianyong, Young Ken H
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Front Oncol. 2019 Mar 1;9:107. doi: 10.3389/fonc.2019.00107. eCollection 2019.
Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoma worldwide, representing 30-40% of non-Hodgkin lymphomas, and is clinically aggressive. Although more than half of patients with DLBCL are cured by using standard first-line immunochemotherapy, the remaining patients are refractory to the first-line therapy or relapse after complete remission and these patients require novel therapeutic approaches. Understanding the pathogenesis of DLBCL is essential for identifying therapeutic targets to tackle this disease. Cell survival dysregulation, a hallmark of cancer, is a characteristic feature of DLBCL. Intrinsic signaling aberrations, tumor microenvironment dysfunction, and viral factors can all contribute to the cell survival dysregulation in DLBCL. In recent years, several novel drugs that target abnormal cell survival pathways, have been developed and tested in clinical trials of patients with DLBCL. In this review, we discuss cell survival dysregulation, the underlying mechanisms, and how to target abnormal cell survival therapeutically in DLBCL patients.
弥漫性大B细胞淋巴瘤(DLBCL)是全球最常见的淋巴瘤类型,占非霍奇金淋巴瘤的30%-40%,具有临床侵袭性。尽管超过一半的DLBCL患者通过使用标准一线免疫化疗得以治愈,但其余患者对一线治疗无效或在完全缓解后复发,这些患者需要新的治疗方法。了解DLBCL的发病机制对于确定治疗该疾病的靶点至关重要。细胞存活失调是癌症的一个标志,也是DLBCL的一个特征。内在信号异常、肿瘤微环境功能障碍和病毒因素都可能导致DLBCL中的细胞存活失调。近年来,几种针对异常细胞存活途径的新型药物已被开发并在DLBCL患者的临床试验中进行了测试。在本综述中,我们讨论了细胞存活失调、潜在机制以及如何在DLBCL患者中针对异常细胞存活进行治疗。