Glade Bender Julia, Cooney Erin M, Kandel Jessica J, Yamashiro Darrell J
Division of Pediatric Oncology, College of Physicians and Surgeons at Columbia University, Irving Pavilion 7, 161 Fort Washington Avenue, New York, NY 10032, USA.
Drug Resist Updat. 2004 Aug-Oct;7(4-5):289-300. doi: 10.1016/j.drup.2004.09.001.
When first conceived, antiangiogenic therapy for cancer offered the possibility of universal efficacy, low toxicity, and little possibility of resistance. Blockade of the vascular endothelial growth factor (VEGF) pathway has yielded the most promising results both in animal models and in patients. However, resistance to VEGF blockade has been found even when given in combination with chemotherapy or other antiangiogenic agents. This resistance is associated with remodeled vasculature and with increased expression of angiogenic factors, such as PDGF-B and angiopoietin-1, which may contribute to vessel stabilization. Future efforts must be directed towards the identification of factors associated with vascular remodeling in order to improve the efficacy of antiangiogenic therapy.
最初设想时，癌症抗血管生成疗法具有普遍有效的可能性、低毒性以及产生耐药性的可能性极小。阻断血管内皮生长因子（VEGF）通路在动物模型和患者中均产生了最有前景的结果。然而，即使与化疗或其他抗血管生成药物联合使用，也发现了对VEGF阻断的耐药性。这种耐药性与血管重塑以及血管生成因子（如血小板衍生生长因子-B和血管生成素-1）表达增加有关，这些因子可能有助于血管稳定。未来的研究必须致力于识别与血管重塑相关的因素，以提高抗血管生成疗法的疗效。
