a School of Clinical Medicine , The University of Queensland , Brisbane , Australia.
b Gallipoli Medical Research Institute , Greenslopes Private Hospital , Brisbane , Australia.
Expert Opin Investig Drugs. 2019 Jan;28(1):7-18. doi: 10.1080/13543784.2019.1551359. Epub 2018 Nov 30.
This study reviews the evidence for the use of Bortezomib (BZB), a first-in-class proteasome inhibitor in advanced Hepatocellular carcinoma (HCC). This review aims to delineate the role of BZB within the management of non-surgical and metastatic HCC, either as an alternative or as an adjunct to the current treatment paradigm.
In addition to BZB pharmacology and mechanism of action, safety and tolerance profiles of the drug obtained from clinical trials are explored. The utility of BZB as a therapeutic agent either alone or in combination with other therapies against HCC, including its application in both preclinical and clinical settings has been reviewed. In particular, we highlight the importance of preclinical evaluation of BZB as a combinatorial agent in synergism with other therapies for the use in the management of HCC.
There has been much interest surrounding the use of BZB, a first-in-class proteasome inhibitor for HCC therapy. The discernment of outcomes of BZB clinical trials for HCC need to take into consideration the disease-specific factors that can affect survival outcomes including patient selection and aetiological differences. Further preclinical testing of BZB in combination with other therapeutic modalities can be important for eliciting enhanced anti-HCC effects.
本研究回顾了硼替佐米(BZB)在晚期肝细胞癌(HCC)中的应用证据。本综述旨在阐明 BZB 在非手术和转移性 HCC 治疗中的作用,无论是作为替代治疗方法还是作为当前治疗模式的辅助手段。
除了 BZB 的药理学和作用机制外,还探讨了临床试验中获得的该药物的安全性和耐受性概况。综述了 BZB 作为单一药物或与其他疗法联合治疗 HCC 的应用,包括其在临床前和临床环境中的应用。特别是,我们强调了在 HCC 管理中作为联合治疗与其他疗法协同作用的组合药物进行临床前评估的重要性。
对于硼替佐米(一种用于 HCC 治疗的首创蛋白酶体抑制剂)的应用,人们一直非常感兴趣。BZB 临床试验的 HCC 结果需要考虑到可能影响生存结果的特定于疾病的因素,包括患者选择和病因差异。进一步在临床前测试 BZB 与其他治疗方式的联合应用,对于引发增强的抗 HCC 效果可能非常重要。