Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
PLoS One. 2013 Jul 2;8(7):e67668. doi: 10.1371/journal.pone.0067668. Print 2013.
Despite progress in locoregional and systemic therapies, patient survival from lung cancer remains a challenge. Receptor tyrosine kinases are frequently implicated in lung cancer pathogenesis, and some tyrosine kinase inhibition strategies have been effective clinically. The EphB4 receptor tyrosine kinase has recently emerged as a potential target in several other cancers. We sought to systematically study the role of EphB4 in lung cancer. Here, we demonstrate that EphB4 is overexpressed 3-fold in lung tumors compared to paired normal tissues and frequently exhibits gene copy number increases in lung cancer. We also show that overexpression of EphB4 promotes cellular proliferation, colony formation, and motility, while EphB4 inhibition reduces cellular viability in vitro, halts the growth of established tumors in mouse xenograft models when used as a single-target strategy, and causes near-complete regression of established tumors when used in combination with paclitaxel. Taken together, these data suggest an important role for EphB4 as a potential novel therapeutic target in lung cancer. Clinical trials investigating the efficacy of anti-EphB4 therapies as well as combination therapy involving EphB4 inhibition may be warranted.
尽管在局部和全身治疗方面取得了进展，但肺癌患者的生存仍然是一个挑战。受体酪氨酸激酶在肺癌的发病机制中经常被涉及，一些酪氨酸激酶抑制策略在临床上已经有效。EphB4 受体酪氨酸激酶最近在其他几种癌症中成为一个潜在的靶点。我们试图系统地研究 EphB4 在肺癌中的作用。在这里，我们证明 EphB4 在肺癌肿瘤中的表达是正常组织的 3 倍，并且在肺癌中经常表现出基因拷贝数的增加。我们还表明，EphB4 的过表达促进细胞增殖、集落形成和运动性，而 EphB4 抑制则减少体外细胞活力，当作为单一靶向策略使用时，阻止小鼠异种移植模型中已建立的肿瘤生长，并在与紫杉醇联合使用时导致已建立的肿瘤几乎完全消退。总的来说，这些数据表明 EphB4 作为肺癌潜在的新型治疗靶点具有重要作用。可能需要进行临床试验，以研究抗 EphB4 治疗的疗效以及涉及 EphB4 抑制的联合治疗。
