Budker Vladimir G, Monahan Sean D, Subbotin Vladimir M
Madison, WI, USA.
410 W. Harrison St, Seattle, WA 98119, USA.
Drug Discov Today. 2014 Dec;19(12):1855-70. doi: 10.1016/j.drudis.2014.08.009. Epub 2014 Aug 28.
Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Many studies have demonstrated anticancer drug effects to be dose-dependent, although dose-escalation studies have resulted in limited survival benefit with increased systemic toxicities. One solution to this has been the idea of loco-regional drug treatments, which offer dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity. Although loco-regional delivery has been most prominent in cancers of the liver, soft tissues and serosal peritoneal malignancies, survival benefits are very far from desirable. This review discusses the evolution of loco-regional treatments, the present approaches and offers rapidly reversible hydrophobization of drugs as the new future direction.
实体肿瘤对药物摄取不足仍然是全身化疗的主要问题。许多研究表明抗癌药物的效果具有剂量依赖性，尽管剂量递增研究在增加全身毒性的情况下仅带来有限的生存获益。解决这一问题的一种方法是局部区域药物治疗的理念，该方法可在肿瘤组织中提供显著更高的药物浓度，同时将全身毒性降至最低。尽管局部区域给药在肝癌、软组织癌和浆膜性腹膜恶性肿瘤中最为突出，但生存获益远不尽人意。本文综述了局部区域治疗的发展历程、当前方法，并提出药物的快速可逆疏水化作为新的未来发展方向。
