文章：

预测抗血管生成药物对恶性肿瘤的疗效

Predicting benefit from anti-angiogenic agents in malignancy

原文发布日期：2006-07-13

DOI: 10.1038/nrc1946

类型: Review Article

开放获取: 否

要点：

1. The addition of anti-angiogenic agents to cytotoxic chemotherapy prolongs patient survival in specific types of cancer.
2. Objective response is a poor estimate of probable benefit from the addition of anti- vascular-endothelial-growth-factor (VEGF) therapy in colorectal cancer.
3. The cost and choice of cancer therapy are increasing dramatically. Therefore, a high likelihood of benefit is needed to justify the use of a targeted anti-angiogenic agent.
4. Anti-angiogenic therapies induce a number of biological and physiological changes in preclinical models of cancer. Similar observations have been reported in human disease, and might function as early indicators of survival benefit.
5. Resistance to anti-VEGF therapy has been noted in human and animal models. Understanding the mechanisms of resistance will be essential when choosing second-line therapies.
6. The optimal biological dose of anti-angiogenic therapy is likely to be lower than the maximum tolerated dose used for cytotoxic chemotherapy. Biomarkers could be needed to guide adequate dose selection and maximize potential benefit.
7. A better understanding of the mechanism of anti-angiogenic therapy is essential to guide the development of biomarkers, drug choice and dosage, and improve survival.

要点翻译：

1. 在细胞毒性化疗中加入抗血管生成药物可延长特定类型癌症患者的生存期。
2. 在结直肠癌中，客观缓解率并不能准确预测加入抗血管内皮生长因子（VEGF）治疗的潜在获益。
3. 癌症治疗的费用和选择正在急剧增加。因此，需要有高度可能的获益来支持使用靶向抗血管生成药物。
4. 抗血管生成治疗在癌症的临床前模型中诱导了多种生物学和生理学变化。在人类疾病中也有类似观察，这些变化可能作为生存获益的早期指标。
5. 在人类和动物模型中均观察到对抗VEGF治疗的耐药。理解耐药机制对于选择二线治疗至关重要。
6. 抗血管生成治疗的最佳生物学剂量可能低于细胞毒性化疗所用的最大耐受剂量。可能需要生物标志物来指导合适的剂量选择，以最大化潜在获益。
7. 更深入地理解抗血管生成治疗的机制对于指导生物标志物、药物选择和剂量的开发，以及提高生存率至关重要。

英文摘要：

A high probability of benefit is desirable to justify the choice of anti-angiogenic therapy from an ever-expanding list of expensive new anticancer agents. However, biomarkers of response to cytotoxic agents are not optimal for predicting benefit from anti-angiogenic drugs. This discussion will focus on both preclinical and clinical research to identify biomarkers for anti-angiogenic therapies that can inform dosing, early clinical benefit, initial drug choice, emerging resistance and second-line treatments.

摘要翻译： 

高概率的获益是合理的，以便从日益增多的昂贵新型抗癌药物中选择抗血管生成疗法。然而，用于预测细胞毒药物疗效的生物标志物并不适用于预测抗血管生成药物的获益。本次讨论将聚焦于临床前和临床研究，以寻找可指导剂量、早期临床获益、初始药物选择、获得性耐药及二线治疗的抗血管生成疗法生物标志物。

原文链接：

Predicting benefit from anti-angiogenic agents in malignancy