Sin Chun-Fung, Man Pui-Hei Marcus
Department of Pathology, University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Oncol. 2021 Dec 23;11:802832. doi: 10.3389/fonc.2021.802832. eCollection 2021.
Acute lymphoblastic leukaemia (ALL) is an aggressive haematolymphoid malignancy. The prognosis of ALL is excellent in paediatric population, however the outcome of relapse/refractory disease is dismal. Adult ALL has less favourable prognosis and relapse/refractory disease is not uncommonly encountered. Bortezomib is the first generation proteasome inhibitor licensed to treat plasma cell myeloma and mantle cell lymphoma with favourable side effect profile. Efficacy of bortezomib had been proven in other solid tumors. Clinical studies showed promising response for proteasome inhibitors in treating relapse/refractory ALL. Thus, proteasome inhibitors are attractive alternative agents for research in treating ALL. In the review article, we will introduce different proteasome inhibitors and their difference in pharmacological properties. Moreover, the mechanism of action of proteasome inhibitors on ALL will be highlighted. Finally, results of various clinical studies on proteasome inhibitors in both paediatric and adult ALL will be discussed. This review article provides the insights on the use of proteasome inhibitors in treating ALL with a summary of mechanism of action in ALL which facilitates future research on its use to improve the outcome of ALL.
急性淋巴细胞白血病(ALL)是一种侵袭性血液淋巴系统恶性肿瘤。ALL在儿童群体中的预后良好,然而复发/难治性疾病的结局却很糟糕。成人ALL的预后较差,复发/难治性疾病并不罕见。硼替佐米是第一代被许可用于治疗浆细胞骨髓瘤和套细胞淋巴瘤的蛋白酶体抑制剂,其副作用较小。硼替佐米在其他实体瘤中的疗效已得到证实。临床研究表明蛋白酶体抑制剂在治疗复发/难治性ALL方面有令人期待的反应。因此,蛋白酶体抑制剂是治疗ALL研究中颇具吸引力的替代药物。在这篇综述文章中,我们将介绍不同的蛋白酶体抑制剂及其药理特性的差异。此外,还将重点介绍蛋白酶体抑制剂对ALL的作用机制。最后,将讨论蛋白酶体抑制剂在儿童和成人ALL中的各种临床研究结果。这篇综述文章提供了关于蛋白酶体抑制剂在治疗ALL方面的见解,并总结了其在ALL中的作用机制,这有助于未来关于其应用的研究,以改善ALL的治疗结局。