Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Cancer J. 2010 Jan-Feb;16(1):33-8. doi: 10.1097/PPO.0b013e3181d38514.
New blood vessel formation plays an important role in breast cancer growth, invasion, and metastasis. Tumor growth is preceded by the development of new blood vessels, which provide a pathway for metastases and nutrients essential for growth. Vascular endothelial growth factor (VEGF) is a key angiogenic mediator that stimulates endothelial cell proliferation and regulates vascular permeability. Highly proliferative tumors, such as those that are negative for the estrogen, progesterone, and HER2/neu receptors have enhanced angiogenesis that supports rapid growth and early metastases and have been found to have high levels of VEGF. Drugs developed to inhibit the angiogenic process may be particularly effective in triple-negative breast cancer. Subset analyses have demonstrated efficacy with combinations of the VEGF antibody bevacizumab in combination with chemotherapy and, to a limited degree, with other antiangiogenic agents. Many targeted biologic agents in development inhibit angiogenesis including those that inhibit the mammalian target of rapamycin, fibroblast growth factor, Notch, hypoxic inducible factor, 2-methoxyestradiol, insulin like growth factor, matrix metalloproteinase, and others. Ongoing studies are focusing on the effects of these agents in triple-negative disease, and there is an urgent need to identify markers that can predict response to specific targeted therapy.
新血管形成在乳腺癌的生长、浸润和转移中起着重要作用。肿瘤生长前会先发展出新的血管，为转移和生长所需的营养物质提供途径。血管内皮生长因子 (VEGF) 是一种关键的血管生成介质，可刺激内皮细胞增殖并调节血管通透性。高度增殖的肿瘤，如雌激素、孕激素和 HER2/neu 受体阴性的肿瘤，其血管生成增强，支持快速生长和早期转移，并且被发现具有高水平的 VEGF。开发用于抑制血管生成过程的药物可能对三阴性乳腺癌特别有效。亚组分析表明，VEGF 抗体贝伐珠单抗与化疗联合使用具有疗效，在一定程度上与其他抗血管生成药物联合使用也具有疗效。许多正在开发中的靶向生物制剂可抑制血管生成，包括那些抑制哺乳动物雷帕霉素靶蛋白、成纤维细胞生长因子、Notch、低氧诱导因子、2-甲氧基雌二醇、胰岛素样生长因子、基质金属蛋白酶等的制剂。正在进行的研究集中在这些药物在三阴性疾病中的作用，迫切需要确定可以预测对特定靶向治疗反应的标志物。
