Mouse models of advanced spontaneous metastasis for experimental therapeutics

• Published in: Nature reviews. Cancer Vol. 11; no. 2; pp. 135 - 141
• Main Authors: Francia, Giulio, Kerbel, Robert S, Cruz-Munoz, William, Man, Shan, Xu, Ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2011; Nature Publishing Group
• Subjects: 631/1647/334/1874/345; 631/67/1059; 631/67/1059/153; 631/67/322; Animals; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Care and treatment; Disease Models, Animal; Drug Evaluation, Preclinical; Excision (Surgery); Health aspects; Metastasis; Mice; Neoplasm Metastasis - drug therapy; Neoplasm Transplantation; opinion-2; Transplantation, Heterologous; Canada
• ISSN: 1474-175X; 1474-1768
• DOI: 10.1038/nrc3001

The successful systemic therapy of advanced visceral metastatic disease remains a daunting challenge, but this therapeutic circumstance has rarely been modelled or studied preclinically. Strategies to develop models of advanced spontaneous metastasis in mice are discussed, and some of the results are summarized. 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.