Zelnak Amelia B, O'Regan Ruth M
Clinical and Translational Breast Cancer Research, Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA.
BioDrugs. 2007;21(4):209-14. doi: 10.2165/00063030-200721040-00001.
Angiogenesis, the process of new blood vessel formation, is required for tumor growth and metastasis. There is substantial preclinical and clinical evidence supporting the central role of angiogenesis in tumor formation and metastasis. Thus, the inhibition of angiogenesis may provide more effective treatment for patients with advanced breast cancer. Several chemotherapeutic and hormonal agents routinely used in the treatment of advanced breast cancer have antiangiogenic properties. Novel antiangiogenic agents targeting the vascular endothelial growth factor (VEGF) ligand and receptor tyrosine kinase inhibitors are being developed. Recently, a large phase III clinical trial demonstrated a significant benefit in progression-free survival with the addition of anti-VEGF monoclonal antibody bevacizumab to paclitaxel for first-line treatment of advanced breast cancer. This study established that antiangiogenic therapy is effective in breast cancer, and additional studies of bevacizumab and other antiangiogenic agents are underway. This article reviews the evidence for the role of angiogenesis in breast cancer pathogenesis, the challenges of developing antiangiogenic agents, and current agents in clinical trials.
血管生成是新血管形成的过程,是肿瘤生长和转移所必需的。有大量临床前和临床证据支持血管生成在肿瘤形成和转移中的核心作用。因此,抑制血管生成可能为晚期乳腺癌患者提供更有效的治疗。几种常用于治疗晚期乳腺癌的化疗和激素药物具有抗血管生成特性。正在研发针对血管内皮生长因子(VEGF)配体和受体酪氨酸激酶抑制剂的新型抗血管生成药物。最近,一项大型III期临床试验表明,在一线治疗晚期乳腺癌时,将抗VEGF单克隆抗体贝伐单抗添加到紫杉醇中可显著提高无进展生存期。这项研究证实抗血管生成疗法在乳腺癌中是有效的,并且正在进行关于贝伐单抗和其他抗血管生成药物的更多研究。本文综述了血管生成在乳腺癌发病机制中的作用证据、开发抗血管生成药物的挑战以及目前临床试验中的药物。