The Molecular & Cellular Biology Research, Sunnybrook Health Science Centre, Toronto, Ontario M4N 3M5, Canada.
Nat Rev Cancer. 2011 Feb;11(2):135-41. doi: 10.1038/nrc3001.
An enduring problem in cancer research is the failure to reproduce highly encouraging preclinical therapeutic findings using transplanted or spontaneous primary tumours in mice in clinical trials of patients with advanced metastatic disease. There are several reasons for this, including the failure to model established, visceral metastatic disease. We therefore developed various models of aggressive multi-organ spontaneous metastasis after surgical resection of orthotopically transplanted human tumour xenografts. In this Opinion article we provide a personal perspective summarizing the prospect of their increased clinical relevance. This includes the reduced efficacy of certain targeted anticancer drugs, the late emergence of spontaneous brain metastases and the clinical trial results evaluating a highly effective therapeutic strategy previously tested using such models.
癌症研究中一个持久存在的问题是，在晚期转移性疾病患者的临床试验中，使用移植或自发的原发性肿瘤在小鼠中重现高度有希望的临床前治疗发现的失败。造成这种情况的原因有几个，包括未能建立已建立的内脏转移性疾病模型。因此，我们开发了各种模型，用于模拟在同种异体移植人肿瘤异种移植物切除后发生的侵袭性多器官自发转移。在这篇观点文章中，我们提供了一个个人视角，总结了它们增加临床相关性的前景。这包括某些靶向抗癌药物疗效降低、自发性脑转移的迟发以及临床试验结果，这些结果评估了之前使用此类模型测试的一种非常有效的治疗策略。
