Davids Matthew S, Brown Jennifer R
Chronic Lymphocytic Leukemia Center, Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
Future Oncol. 2014 May;10(6):957-67. doi: 10.2217/fon.14.51.
Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton's tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and Waldenström's macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies.
依鲁替尼（原称PCI-32765）是一种强效的布鲁顿酪氨酸激酶共价抑制剂，布鲁顿酪氨酸激酶是B细胞受体下游的一种激酶，对B细胞的存活和增殖至关重要。在临床前研究中，依鲁替尼与布鲁顿酪氨酸激酶具有高亲和力结合，导致B细胞受体信号传导受到抑制、B细胞活化降低并诱导细胞凋亡。在临床研究中，依鲁替尼耐受性良好，并在多种血液系统恶性肿瘤中显示出显著的抗肿瘤活性，最显著的是慢性淋巴细胞白血病（CLL）和套细胞淋巴瘤（MCL），从而获得美国食品药品监督管理局（US FDA）对复发性CLL和MCL的批准。正在进行的研究正在评估依鲁替尼在其他类型的非霍奇金淋巴瘤中的作用，如弥漫性大B细胞淋巴瘤和华氏巨球蛋白血症，在更大规模的CLL和MCL III期研究中，以及在与单克隆抗体和化疗的联合研究中。未来的研究将把依鲁替尼与目前正在血液系统恶性肿瘤中开发的其他有前景的新型药物联合使用。
