Division of Hematology/Oncology, Tisch Cancer Institute & Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Future Oncol. 2013 Oct;9(10):1549-71. doi: 10.2217/fon.13.113.
Lymphoma is the fifth most common cancer in the USA. Most lymphomas are classified as non-Hodgkin's lymphoma, and nearly 95% of these cancers are of B-cell origin. B-cell receptor (BCR) surface expression and BCR functional signaling are critical for survival and proliferation of both healthy B cells, as well as most B-lymphoma cells. Agents that inhibit various components of the BCR signaling pathway, as well as parallel signaling pathways, are currently in clinical trials for the treatment of various lymphoma subtypes, including those targeting isoforms of PI3K, mTOR and BTK. In this review, we describe the signaling pathways in healthy mature B cells, the aberrant signaling in lymphomatous B cells and the rationale for clinical trials of agents targeting these pathways as well as the results of clinical trials to date. We propose that the entry into a kinase inhibitor era of lymphoma therapy will be as transformative for our patients as the advent of the antibody or chemotherapy era before it.
淋巴瘤是美国第五大常见癌症。大多数淋巴瘤被归类为非霍奇金淋巴瘤，而这些癌症中近 95%是 B 细胞来源的。B 细胞受体（BCR）表面表达和 BCR 功能信号对于健康 B 细胞以及大多数 B 细胞淋巴瘤细胞的存活和增殖至关重要。目前，抑制 BCR 信号通路以及平行信号通路的各种成分的药物正在临床试验中用于治疗各种淋巴瘤亚型，包括针对 PI3K、mTOR 和 BTK 同工型的药物。在这篇综述中，我们描述了健康成熟 B 细胞中的信号通路、淋巴瘤 B 细胞中的异常信号以及针对这些通路的药物临床试验的原理以及迄今为止的临床试验结果。我们提出，淋巴瘤治疗进入激酶抑制剂时代将像之前的抗体或化疗时代一样，为我们的患者带来变革。
