Kelly Ronan J, Billemont Bertrand, Rixe Olivier
National Cancer Institute, Medical Oncology Branch, Center for Cancer Research, NIH, Bethesda, MD 20892, USA.
Target Oncol. 2009 Apr;4(2):121-33. doi: 10.1007/s11523-009-0109-x. Epub 2009 May 6.
The use of molecular targeted therapies for the treatment of cancer has increased over the last decade. The benefits of these compounds in terms of efficacy are often relatively modest and counter balanced by the occurrence of significant toxicities. Many of these newer agents used in clinical practice lack specificity and selectivity and have a propensity to inhibit multiple targets. The biological consequences of multi-kinase activity are poorly defined and numerous class-specific toxicities have been described. The kidney is an organ where most of these targeted pathways are expressed. Preclinical data and human renal biopsies have generated an understanding of the mechanisms involved in how targeted agents can cause renal toxicity. This review article discusses the observed nephrotoxicity with this burgeoning class of therapeutics and reviews both the biological reasons for its occurrence and possible ways to prevent significant renal damage.
在过去十年中,分子靶向疗法在癌症治疗中的应用有所增加。这些化合物在疗效方面的益处往往相对有限,且被显著毒性的出现所抵消。临床实践中使用的许多这类新型药物缺乏特异性和选择性,倾向于抑制多个靶点。多激酶活性的生物学后果尚不明确,且已描述了众多类别特异性毒性。肾脏是表达大多数这些靶向通路的器官。临床前数据和人类肾活检已使人们对靶向药物导致肾毒性的相关机制有了一定了解。本文综述讨论了这类新兴疗法所观察到的肾毒性,并回顾了其发生的生物学原因以及预防严重肾损伤的可能方法。