Weidle Ulrich H, Birzele Fabian, Tiefenthaler Georg
Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.
Roche Pharma Research and Early Development, Pharmaceutical Sciences, Basel, Switzerland.
Cancer Genomics Proteomics. 2018 Jul-Aug;15(4):225-238. doi: 10.21873/cgp.20081.
In this review we summarize the principles of anti-metastatic therapy with selected serpin family proteins, such as pigment epithelial-derived factor (PEDF) and maspin, as well as inter α-trypsin inhibitor (IαIs) light chains (bikunin) and heavy chains (ITIHs). Case-by-case, antimetastatic activity may be dependent or independent of the protease-inhibitory activity of the corresponding proteins. We discuss the incidence of target deregulation in different tumor entities, mechanisms of deregulation, context-dependent functional issues as well as in vitro and in vivo target validation studies with transfected tumor cells or recombinant protein as anti-metastatic agents. Finally, we comment on possible clinical evaluation of these proteins in adjuvant therapy.
在本综述中，我们总结了使用选定的丝氨酸蛋白酶抑制剂家族蛋白（如色素上皮衍生因子（PEDF）和乳腺丝抑蛋白）以及α-胰蛋白酶抑制剂（IαIs）轻链（比库宁）和重链（ITIHs）进行抗转移治疗的原则。具体而言，抗转移活性可能取决于或独立于相应蛋白质的蛋白酶抑制活性。我们讨论了不同肿瘤实体中靶点失调的发生率、失调机制、背景依赖性功能问题以及使用转染肿瘤细胞或重组蛋白作为抗转移剂的体外和体内靶点验证研究。最后，我们对这些蛋白在辅助治疗中的可能临床评估进行了评论。
