Department of Orthopaedics, University of Melbourne, and St. Vincent's Hospital Melbourne, L3-Daly Wing, 35 Victoria Pde., Fitzroy, Melbourne, VIC 3065 Australia.
Mol Cancer Ther. 2009 Dec;8(12):3173-80. doi: 10.1158/1535-7163.MCT-09-0685.
In the past few years, the pro-apoptotic molecule Bim has attracted increasing attention as a plausible target for tumor therapy. A variety of normal and pathological systems regulated by Bim, dependent on cell type, apoptotic stimulation, and chemotherapeutic agents, have been documented. Bim promotes anoikis of many tumor cells, such as lung cancer, breast cancer, osteosarcoma, and melanoma. Various chemotherapeutic agents use Bim as a mediating executioner of cell death. Hence, Bim suppression supports metastasis and chemoresistance. Imatinib, gefitinib, bortezomib, and Bim protein itself are spotlighted as current and future Bim-targeting therapeutic agents. The potential benefits of Bim-targeted therapies are selectivity of treatment for tumor cells and reduction in tumor-associated phenomena such as chemoresistance and metastasis. Thus, Bim-targeting therapies may provide more effective and unique tumor management modalities in future. This review article discusses all these issues.
在过去的几年中,促凋亡分子 Bim 作为肿瘤治疗的一个合理靶点引起了越来越多的关注。已经有大量的文献记录了 Bim 调节的各种正常和病理系统,这取决于细胞类型、凋亡刺激和化疗药物。Bim 促进许多肿瘤细胞的失巢凋亡,如肺癌、乳腺癌、骨肉瘤和黑色素瘤。各种化疗药物利用 Bim 作为细胞死亡的中介执行者。因此,Bim 的抑制支持转移和化疗耐药性。伊马替尼、吉非替尼、硼替佐米和 Bim 蛋白本身是目前和未来针对 Bim 的治疗药物的焦点。针对 Bim 的治疗的潜在好处是对肿瘤细胞的治疗具有选择性,并减少与肿瘤相关的现象,如化疗耐药性和转移。因此,针对 Bim 的治疗可能在未来提供更有效和独特的肿瘤管理方式。本文综述了所有这些问题。