文章：

实体肿瘤中的药物渗透

Drug penetration in solid tumours

原文发布日期：2006-08-01

DOI: 10.1038/nrc1893

类型: Review Article

开放获取: 否

要点：

1. Most studies of tumour resistance to anticancer drugs consider only cellular and/or genetic causes operative at the level of a single cell.
2. Many anticancer drugs have limited distribution from blood vessels in solid tumours, which limits their effectiveness.
3. Large distances between blood vessels in solid tumours, the composition of the extracellular matrix, cell–cell adhesion, high interstitial fluid pressure, lack of convection, drug metabolism and binding contribute to limited drug distribution.
4. New in vitro and in vivo techniques enable quantitative assessment of drug penetration.
5. Several strategies have the potential to improve the distribution of anticancer drugs in tumours, and thereby improve their therapeutic index.
6. Drug development strategies where molecules are designed or libraries screened for optimal drug penetration would aid the development of more effective anticancer drugs.

要点翻译：

1. 大多数关于肿瘤对抗癌药物耐药性的研究仅关注单细胞层面上的细胞和/或遗传因素。
2. 许多抗癌药物在实体瘤中从血管分布有限，这限制了它们的疗效。
3. 实体瘤中血管间距离大、细胞外基质组成、细胞间粘附、高间质液压力、缺乏对流、药物代谢和结合等因素导致药物分布受限。
4. 新的体外和体内技术能够定量评估药物渗透。
5. 若干策略有望改善抗癌药物在肿瘤中的分布，从而提高其治疗指数。
6. 在药物开发策略中，通过设计分子或筛选库以优化药物渗透，将有助于开发更有效的抗癌药物。

英文摘要：

To be most effective anticancer drugs must penetrate tissue efficiently, reaching all the cancer cells that comprise the target population in a concentration sufficient to exert a therapeutic effect. Most research into the resistance of cancers to chemotherapy has concentrated on molecular mechanisms of resistance, whereas the role of limited drug distribution within tumours has been neglected. We summarize the evidence that indicates that the distribution of many anticancer drugs in tumour tissue is incomplete, and we suggest strategies that might be used either to improve drug penetration through tumour tissue or to select compounds based on their abilities to penetrate tissue, thereby increasing the therapeutic index.

摘要翻译： 

为了发挥最大疗效，抗癌药物必须高效穿透组织，以足够浓度抵达所有癌细胞。目前关于化疗耐药的研究多聚焦于分子机制，而忽视了药物在肿瘤内分布受限的问题。我们总结了多项证据，表明许多抗癌药物在肿瘤组织中的分布并不完全，并提出可能改善药物渗透或基于渗透能力筛选化合物的策略，以提高治疗指数。

原文链接：

Drug penetration in solid tumours