Hematology Branch, National Heart, Lung, Blood Institute, National Institutes of Health, Bldg. 10, CRC 3-5140, 10 Center Drive, Bethesda, MD, 20892-1202, USA.
Adv Exp Med Biol. 2013;792:259-91. doi: 10.1007/978-1-4614-8051-8_12.
The B cell antigen receptor (BCR) and its downstream pathways are pivotal in the pathogenesis of chronic lymphocytic leukemia (CLL). Recently, inhibitors of kinases in the BCR pathway have shown promising clinical activity in CLL. Based upon these results, the treatment paradigm for CLL will likely undergo major changes. The kinases essential for BCR signal transduction, which are emerging as targets for CLL treatment, and the specific inhibitors under development are the focus of this chapter. In particular, the BTK inhibitor ibrutinib and the PI3K inhibitor idelalisib (GS-1101) are two evolving targeted therapies with the most mature clinical data.
B 细胞抗原受体 (BCR) 及其下游途径在慢性淋巴细胞白血病 (CLL) 的发病机制中起着关键作用。最近，BCR 途径激酶抑制剂在 CLL 中的临床活性令人瞩目。基于这些结果，CLL 的治疗模式可能会发生重大变化。BCR 信号转导所必需的激酶，这些激酶正成为 CLL 治疗的靶点，以及正在开发的特定抑制剂，是本章的重点。特别是，BTK 抑制剂伊布替尼和 PI3K 抑制剂idelalisib (GS-1101) 是两种具有最成熟临床数据的不断发展的靶向治疗药物。
