Actelion Pharmaceuticals, Ltd, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
Semin Cancer Biol. 2012 Jun;22(3):261-71. doi: 10.1016/j.semcancer.2012.03.005. Epub 2012 Mar 30.
Disseminated tumor cells are present in many patients at diagnosis. At a time when the disseminated disease becomes prominent, patients have already been treated with many cycles of therapy to which their metastases were also exposed. These metastases have genetically evolved from primary tumors. Furthermore, their interaction with the tissue microenvironment plays an important role in all phases of disease development. These facts have only partially been taken into consideration when profiling anti-cancer compounds foreseen to treat patients with disseminated metastatic disease. In this perspective, we discuss the unique features of metastatic disease and review the model systems available for drug profiling. Based on an analysis of how compounds are profiled today in pre-clinical models of metastatic disease and what would be desirable and possible with the present know-how, we recommend a refined profiling process to validate drugs with potential to treat patients with overt metastatic disease.
在诊断时，许多患者体内就存在播散的肿瘤细胞。当播散的疾病变得明显时，患者已经接受了许多轮的治疗，这些治疗也使他们的转移灶暴露于其中。这些转移灶是从原发性肿瘤中遗传进化而来的。此外，它们与组织微环境的相互作用在疾病发展的所有阶段都起着重要作用。在预测用于治疗播散性转移性疾病患者的抗癌化合物时，这些事实仅部分得到了考虑。从这个角度出发，我们讨论了转移性疾病的独特特征，并回顾了现有的药物分析模型系统。基于对目前在转移性疾病的临床前模型中对化合物进行分析的方式以及利用现有专业知识实现理想情况的分析，我们建议采用一种经过改进的分析流程，以验证具有治疗明显转移性疾病患者潜力的药物。
