Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: A bridge to the clinic

被引:449
作者
Hoffman, RM [1 ]
机构
[1] AntiCanc Inc, San Diego, CA 92111 USA
关键词
metastasis; surgical orthotopic implantation; immunodeficient mice; green fluorescent protein; tumor imaging; clinically-relevant models;
D O I
10.1023/A:1006326203858
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Currently used rodent tumor models, including transgenic tumor models, or subcutaneously-growing human tumors in immunodeficient mice, do not sufficiently represent clinical cancer, especially with regard to metastasis and drug sensitivity. In order to obtain clinically accurate models, we have developed the technique of surgical orthotopic implantation (SOI) to transplant histologically-intact fragments of human cancer, including tumors taken directly from the patient, to the corresponding organ of immunodeficient rodents. It has been demonstrated in 70 publications describing 10 tumor types that SOI allows the growth and metastatic potential of the transplanted tumors to be expressed and reflects clinical cancer. Unique clinically-accurate and relevant SOI models of human cancer for antitumor and antimetastatic drug discovery include: spontaneous SOI bone metastatic models of prostate cancer, breast cancer and lung cancer; spontaneous SOI liver and lymph node ultra-metastatic model of colon cancer, metastatic models of pancreatic, stomach, ovarian, bladder and kidney cancer. Comparison of the SOI models with transgenic mouse models of cancer indicate that the SOI models have more features of clinical metastatic cancer. Cancer cell lines have been stably transfected with the jellyfish Aequorea victoria green fluorescent protein (GFP) in order to track metastases in fresh tissue at ultra-high resolution and externally image metastases in the SOI models. Effective drugs can be discovered and evaluated in the SOI models utilizing human tumor cell lines and patient tumors. These unique SOI models have been used for innovative drug discovery and mechanism studies and serve as a bridge linking pre-clinical and clinical research and drug development.
引用
收藏
页码:343 / 359
页数:17
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