Yamamura Masahiro, Hirai Toshihiro, Yamaguchi Yoshiyuki
Department of Clinical Oncology, Kawasaki Medical School.
Nihon Rinsho. 2010 Jun;68(6):1079-84.
The ubiquitin-proteasome pathway plays an important role in the regulation of cellular proteins with regard to cell cycle control, transcription, apoptosis, cell adhesion, angiogenesis and tumor growth. Proteasome inhibition is a novel approach to the treatment of solid tumors. Bortezomib is the first proteasome inhibitor evaluated in clinical trials. In vitro experiments have shown that bortezomib treatment has a cytotoxic effect on various breast, colorectal, ovarian, pancreatic, prostate, lung and oral cancer cells. Here, the usefulness of proteasome inhibitor for cancer therapy is discussed, and a review of preclinical and clinical studies on proteasome inhibitors alone and in combination with conventional chemotherapy is included.
泛素-蛋白酶体途径在细胞周期调控、转录、细胞凋亡、细胞黏附、血管生成和肿瘤生长等方面的细胞蛋白质调节中发挥着重要作用。蛋白酶体抑制是治疗实体瘤的一种新方法。硼替佐米是首个在临床试验中得到评估的蛋白酶体抑制剂。体外实验表明,硼替佐米治疗对各种乳腺癌、结直肠癌、卵巢癌、胰腺癌、前列腺癌、肺癌和口腔癌细胞具有细胞毒性作用。本文讨论了蛋白酶体抑制剂在癌症治疗中的效用,并综述了蛋白酶体抑制剂单独使用以及与传统化疗联合使用的临床前和临床研究。