Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.
Cancer Chemother Pharmacol. 2018 Feb;81(2):227-243. doi: 10.1007/s00280-017-3489-0. Epub 2017 Nov 28.
Targeting of the protein degradation pathway, in particular, the ubiquitin-proteasome system, has emerged as an attractive novel cancer chemotherapeutic modality. Although proteasome inhibitors have been most successfully applied in the treatment of hematological malignancies, they also received continuing interest for the treatment of solid tumors. In this review, we summarize the current positioning of proteasome inhibitors in the treatment of common solid malignancies (e.g., lung, colon, pancreas, breast, and head and neck cancer), addressing topics of their mechanism(s) of action, predictive factors and molecular mechanisms of resistance.
靶向蛋白降解途径,特别是泛素-蛋白酶体系统,已成为一种有吸引力的新型癌症化学治疗模式。尽管蛋白酶体抑制剂在治疗血液系统恶性肿瘤方面最为成功,但它们在治疗实体瘤方面也受到持续关注。在这篇综述中,我们总结了蛋白酶体抑制剂在治疗常见实体恶性肿瘤(如肺癌、结肠癌、胰腺癌、乳腺癌和头颈部癌)中的定位,涉及它们的作用机制、预测因素和耐药性的分子机制等方面。