Antiangiogenic therapy: impact on invasion, disease progression, and metastasis.
Antiangiogenic therapy: impact on invasion, disease progression, and metastasis.
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DOI：
10.1038/nrclinonc.2011.21
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发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Kerbel RS
中科院分区：
文献类型：
--
作者：
Ebos JM;Kerbel RS
与对照组相比，针对血管内皮生长因子途径的抗血管生成药物已经减缓了一些患者的转移性疾病进展，导致了无进展生存(PFS)和总体生存益处。然而，结果比大多数临床前试验预测的要温和得多，而且PFS的好处往往并不伴随着总体生存率的改善。关于耐药性的基础和临床前预测性模型的局限性，以及抗血管生成治疗后疾病进展的性质是否不同于经典的细胞毒治疗--特别是治疗是否可能导致更多侵袭性或转移性行为，已经出现了一些问题。此外，由于最近抗血管生成疗法在早期疾病患者中的临床试验失败，以及在围手术期新辅助和辅助环境中正在进行的数百项试验，现在人们更多地意识到在这些研究之前缺乏适当的临床前试验。改善对转移性疾病所有阶段的临床前评估应该是未来抗血管生成药物发现和开发的优先事项。
Antiangiogenic drugs targeting the VEGF pathway have slowed metastatic disease progression in some patients, leading to progression-free survival (PFS) and overall survival benefits compared with controls. However, the results are more modest than predicted by most preclinical testing and benefits in PFS are frequently not accompanied by overall survival improvements. Questions have emerged about the basis of drug resistance and the limitations of predictive preclinical models, and also about whether the nature of disease progression following antiangiogenic therapy is different to classic cytotoxic therapies—in particular whether therapy may lead to more invasive or metastatic behavior. In addition, because of recent clinical trial failures of antiangiogenic therapy in patients with early-stage disease, and the fact that there are hundreds of trials underway in perioperative neoadjuvant and adjuvant settings, there is now greater awareness about the lack of appropriate preclinical testing that preceded these studies. Improved preclinical assessment of all stages of metastatic disease should be a priority for future antiangiogenic drug discovery and development.