Pharmacokinetic strategies to improve drug penetration and entrapment within solid tumors
Pharmacokinetic strategies to improve drug penetration and entrapment within solid tumors
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DOI：
10.1016/j.jconrel.2015.08.055
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发表时间：
2015-12-10
影响因子：
10.8
通讯作者：
Torchilin, Vladimir P.
中科院分区：
文献类型：
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作者：
Al-Abd, Ahmed M.;Aljehani, Zekra K.;Torchilin, Vladimir P.
尽管发现了大量的抗癌药物，但自20世纪中叶以来，癌症仍然是导致死亡的主要原因之一。实体瘤具有高度的遗传不稳定性和治疗耐药性的出现。几乎所有已批准的抗癌药物都出现了肿瘤耐药性，而且很可能新发现的抗癌药物也会出现肿瘤耐药性。利用药代动力学方法增加实体肿瘤腔室内的抗癌药物浓度并延长其包裹时间，可能会在分子药效学水平上减少耐药性出现的可能性，甚至可能逆转肿瘤耐药性。一些新的治疗方式，如节拍疗法，血管生成抑制剂，血管破坏剂和肿瘤启动已被引入，以改善实体瘤的治疗效果。在当前的综述中，我们将讨论这些治疗方式的药代动力学方面，以及其他较老的治疗方式，如细胞外基质溶解剂、细胞外基质合成抑制剂、化疗栓塞和细胞外排泵抑制。其中许多策略呈现出不同程度的成功/失败；然而，根据它们对肿瘤内药代动力学的影响重新分配这些模式可能会提高对它们的理解和治疗效果。(C) 2015 Elsevier B.V.版权所有
Despite the discovery of a large number of anticancer agents, cancer still remains among the leading causes of death since the middle of the twentieth century. Solid tumors possess a high degree of genetic instability and emergence of treatment resistance. Tumor resistance has emerged for almost all approved anticancer drugs and will most probably emerge for newly discovered anticancer agents as well. The use of pharmacokinetic approaches to increase anticancer drug concentrationswithin the solid tumor compartment and prolong its entrapment might diminish the possibility of resistance emergence at themolecular pharmacodynamic level andmight even reverse tumor resistance. Several novel treatment modalities such as metronomic therapy, angiogenesis inhibitors, vascular disrupting agents and tumor priming have been introduced to improve solid tumor treatment outcomes. In the current reviewwe will discuss the pharmacokinetic aspect of these treatment modalities in addition to other older treatment modalities, such as extracellular matrix dissolving agents, extracellular matrix synthesis inhibitors, chemoembolization and cellular efflux pump inhibition. Many of these strategies showed variable degrees of success/failure; however, reallocating these modalities based on their influence on the intratumoral pharmacokinetics might improve their understanding and treatment outcomes. (C) 2015 Elsevier B.V. All rights reserved.