Gkretsi Vasiliki, Zacharia Lefteris C, Stylianopoulos Triantafyllos
Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.
Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus.
Trends Cancer. 2017 Sep;3(9):621-630. doi: 10.1016/j.trecan.2017.07.006. Epub 2017 Aug 23.
Inefficient delivery of drugs is a main cause of chemotherapy failure in hypoperfused tumors. To enhance perfusion and drug delivery in these tumors, two strategies have been developed: vascular normalization, aiming at normalizing tumor vasculature and blood vessel leakiness, and stress alleviation, aiming at decompressing tumor vessels. Vascular normalization is based on anti-angiogenic drugs, whereas stress alleviation is based on stroma-depleting agents. We present here an alternative approach to normalize tumor vasculature, taking into account that malignant tumors tend to develop at sites of chronic inflammation. Similarly to tumor vessel leakiness, inflammation is also characterized by vascular hyperpermeability. Therefore, testing the ability of anti-inflammatory agents, such as non-steroidal anti-inflammatory drugs (NSAIDs) or inflammation resolution mediators, as an alternative means to increase tumor drug delivery might prove promising.
药物递送效率低下是灌注不足肿瘤化疗失败的主要原因。为了增强这些肿瘤的灌注和药物递送,已开发出两种策略:血管正常化,旨在使肿瘤血管系统和血管渗漏正常化;以及压力缓解,旨在减轻肿瘤血管压力。血管正常化基于抗血管生成药物,而压力缓解基于基质消耗剂。考虑到恶性肿瘤倾向于在慢性炎症部位发展,我们在此提出一种使肿瘤血管系统正常化的替代方法。与肿瘤血管渗漏类似,炎症也以血管高通透性为特征。因此,测试抗炎剂(如非甾体抗炎药或炎症消退介质)作为增加肿瘤药物递送的替代手段的能力可能很有前景。