Tumor refractoriness to anti-VEGF therapy.
Tumor refractoriness to anti-VEGF therapy.
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DOI：
10.18632/oncotarget.8694
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Ribatti D
中科院分区：
文献类型：
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作者：
Ribatti D
血管内皮生长因子（Vascular endothelial growth factor， VEGF）被认为是参与肿瘤血管生成和转移形成的最有效的细胞因子。针对VEGF及其受体的抗血管生成治疗的临床结果非常温和，导致总生存期的适度改善。临床结果与耐药性的发展以及侵袭和转移风险的增加有关。在这篇文章中，我分析了VEGF通路抑制剂耐药的主要机制，包括肿瘤血管的正常化、缺氧、炎症细胞和未成熟骨髓细胞的募集、肿瘤血管形成的替代机制、肿瘤内皮细胞的基因组不稳定性。在这种背景下，抗血管生成治疗的概念和策略应该被广泛地重新考虑和重新评估。特别是，需要根据药代动力学和药效学数据合理组合抗血管生成药物以克服耐药性，确定抗vegf药物的最佳持续时间和时间表非常重要。
Vascular endothelial growth factor (VEGF) has been identified as the most potent cytokine involved in tumor angiogenesis and metastasis formation. Clinical results of anti-angiogenic therapies targeting VEGF and its receptors are very modest, resulting in a moderate improvement of overall survival. The clinical outcome is associated with the development of resistance and the increased risk of invasion and metastasis. In this article, I have analyzed the principal mechanisms of resistance to VEGF pathway inhibitors, including normalization of tumor blood vessels, hypoxia, recruitment of inflammatory cells and immature myeloid cells, alternative mechanisms of tumor vessel formation, genomic instability of tumor endothelial cells. In this context, the concept and strategies of anti-angiogenic therapies should be extensively re-considered and re-evaluated. In particular, rational combinations of anti-angiogenic agents based on pharmacokinetic and pharmacodynamics data are needed to overcome resistance and it is extremely important to determine the optimal duration and scheduling of anti-VEGF agents.