Rottenberg Sven, Jonkers Jos
Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Drug Resist Updat. 2008 Feb-Apr;11(1-2):51-60. doi: 10.1016/j.drup.2007.11.002. Epub 2007 Dec 31.
Resistance to anti-cancer drugs is a major obstacle in successful treatment of cancer. Multidrug resistance is not only observed with clinically established chemotherapeutics, but also with novel targeted therapies. Although a range of drug resistance mechanisms have been identified up till now, for most drugs it is still controversial which mechanisms are responsible for resistance and therapy failure in patients. Hence, the development of strategies to circumvent drug resistance is often unfocused. Since several years genetically engineered mouse models have been generated which develop tumors that closely resemble cancer in humans. We argue that such models can be used to investigate relevant in vivo mechanisms of resistance. This includes the analysis of intrinsic and acquired resistance, and the characterization of residual cells which survive the treatment. In such model systems different drugs and therapy combinations can be optimized prior to clinical trials.
抗癌药物耐药性是癌症成功治疗的主要障碍。多药耐药不仅在临床已确立的化疗药物中出现，在新型靶向治疗中也有发现。尽管到目前为止已经确定了一系列耐药机制，但对于大多数药物而言，究竟哪些机制导致患者耐药和治疗失败仍存在争议。因此，规避耐药性策略的开发往往缺乏针对性。几年来，已经构建了基因工程小鼠模型，这些模型所产生的肿瘤与人类癌症极为相似。我们认为，此类模型可用于研究相关的体内耐药机制。这包括对固有耐药性和获得性耐药性的分析，以及对治疗后存活的残余细胞的特性研究。在这样的模型系统中，可以在临床试验之前优化不同的药物和治疗组合。
