Tissue Factor as a Novel Target for Treatment of Breast Cancer
Tissue Factor as a Novel Target for Treatment of Breast Cancer
复制标题
DOI：
10.1634/theoncologist.2012-0322
复制
发表时间：
2013-01-01
期刊：
影响因子：
5.8
通讯作者：
Bromberg, Michael
中科院分区：
文献类型：
--
作者：
Cole, Marion;Bromberg, Michael
组织因子（TF）是一种47kda的跨膜糖蛋白，当与VIIa因子（FVIIa）结合时，可启动血液凝固，在多种肿瘤类型中表达。TF已被证明在细胞信号传导、炎症、血管生成以及肿瘤生长和转移中发挥作用。TF信号通路的激活涉及介导许多肿瘤细胞类型的功能，并导致TF成为治疗多种恶性肿瘤的潜在靶点。乳腺癌细胞中TF-FVIIa复合物的形成已被证明具有抗凋亡作用，并在肿瘤生长和转移中发挥关键作用。抑制tnf介导的PAR2信号通路可抑制乳腺癌的生长，而PAR2缺乏可延缓小鼠自发性乳腺癌的发展。TF在三阴性乳腺癌（TNBC）中表达，TNBC是一种侵袭性乳腺癌，目前缺乏可用的靶点。针对TF的各种方法已经被研究，包括免疫偶联物或标记物、抗TF抗体、TF途径抑制剂、靶向光动力疗法和microrna。这些研究可能会让位于有希望的乳腺癌临床治疗，特别是在三阴癌中，这是相对较少的有效治疗选择。肿瘤学家2013；18:14-18
Tissue factor (TF), a 47-kDa transmembrane glycoprotein that initiates blood coagulation when complexed with factor VIIa (FVIIa), is expressed in several tumor types. TF has been shown to play a role in cell signaling, inflammation, angiogenesis, as well as tumor growth and metastasis. Activation of the TF signaling pathway has been implicated in mediating the function of many tumor cell types and has led to TF as a potential target in the treatment of several malignancies. Formation of the TF-FVIIa complex in breast cancer cells has been shown to exert an antiapoptotic effect and play a key role in tumor growth and metastasis. Breast cancer growth is suppressed by inhibition of TF-mediated PAR2 signaling, and deficiency in PAR2 delays spontaneous breast cancer development in mice. TF is expressed in triple-negative breast cancer (TNBC), an aggressive type of breast cancer in which there is currently a paucity of available targets. Various methods of targeting TF have been investigated and include immunoconjugates or icons, anti-TF antibodies, TF pathway inhibitors, targeted photodynamic therapy, and microRNAs. These investigations may give way to promising clinical therapies for breast cancer, especially in TNBC, for which there are relatively few effective treatment options. The Oncologist 2013;18:14-18