Calithera Biosciences, Inc., South San Francisco, California 94080, USA.
Clin Cancer Res. 2012 Jan 1;18(1):15-20. doi: 10.1158/1078-0432.CCR-11-0853. Epub 2011 Oct 21.
With the approval by the U.S. Food and Drug Administration of bortezomib for the treatment of multiple myeloma and mantle cell lymphoma, the proteasome was clinically validated as a target in oncology. The proteasome is part of a complex cellular pathway that controls the specificity and rate of degradation of the majority of proteins in the cell. The search for additional drug targets in the proteasomal pathway is ongoing. In parallel, the next generation of proteasome inhibitors, exhibiting some properties distinct from that of bortezomib, are currently being studied in clinical trials. The key question will be whether these distinctions can improve upon the clinical efficacy and safety standards established by bortezomib and refine our understanding of the mechanism by which proteasome inhibitors are effective in the treatment of cancer.
在美国食品和药物管理局批准硼替佐米用于多发性骨髓瘤和套细胞淋巴瘤的治疗后，蛋白酶体在肿瘤学领域被临床验证为一个靶点。蛋白酶体是控制细胞中大多数蛋白质降解特异性和速率的复杂细胞途径的一部分。目前正在寻找蛋白酶体途径中的其他药物靶点。与此同时，具有与硼替佐米不同特性的下一代蛋白酶体抑制剂正在临床试验中进行研究。关键问题将是这些差异是否能够提高硼替佐米确立的临床疗效和安全性标准，并深化我们对蛋白酶体抑制剂在癌症治疗中有效的机制的理解。
