Centre for Cancer Research and Cell Biology, Queen's University Belfast, Ground Floor, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL.
J Cell Commun Signal. 2011 Jun;5(2):101-10. doi: 10.1007/s12079-011-0121-7. Epub 2011 Jan 31.
The ubiquitin proteasome pathway plays a critical role in regulating many processes in the cell which are important for tumour cell growth and survival. Inhibition of proteasome function has emerged as a powerful strategy for anti-cancer therapy. Clinical validation of the proteasome as a therapeutic target was achieved with bortezomib and has prompted the development of a second generation of proteasome inhibitors with improved pharmacological properties. This review summarises the main mechanisms of action of proteasome inhibitors in cancer, the development of proteasome inhibitors as therapeutic agents and the properties and progress of next generation proteasome inhibitors in the clinic.
泛素蛋白酶体途径在调节细胞中的许多过程中起着关键作用,这些过程对肿瘤细胞的生长和存活很重要。抑制蛋白酶体的功能已成为抗癌治疗的一种有效策略。硼替佐米的临床验证了蛋白酶体作为治疗靶点,并促使开发了具有改善的药理学特性的第二代蛋白酶体抑制剂。本文综述了蛋白酶体抑制剂在癌症中的主要作用机制、蛋白酶体抑制剂作为治疗剂的发展以及下一代蛋白酶体抑制剂在临床中的特性和进展。