Human Tumor Xenograft Models for Preclinical Assessment of Anticancer Drug Development

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Xenograft models of human cancer play an important role in the screening and evaluation of candidates for new anticancer agents. The models, which are derived from human tumor cell lines and are classified according to the transplant site, such as ectopic xenograft and orthotopic xenograft, are still utilized to evaluate therapeutic efficacy and toxicity. The metastasis model is modified for the evaluation and prediction of cancer progression. Recently, animal models are made from patient-derived tumor tissue. The patient-derived tumor xenograft models with physiological characters similar to those of patients have been established for personalized medicine. In the discovery of anticancer drugs, standard animal models save time and money and provide evidence to support clinical trials. The current strategy for using xenograft models as an informative tool is introduced. INTRODUCTION Animal models play an important role in drug development and studies of molecular biological mechanisms. Historically, the coal tar-induced skin cancer model in rabbit triggered the development of a carcinogen-induced mouse model. Various animal models have been established as an evaluation tool for the prediction of carcinogens and investigation of carcinogenic mechanisms. However, the approach of using chronic exposure to a carcinogen is timeintensive and expensive, thus limiting its application in drug development. Nevertheless, mouse models are still more attractive than big animal models because of the low cost, ease-of-handling and known genetic information. More recently, a syngenic mouse model injected with murine cell lines has been developed. The advantages of this model are reproducibility, ability to easily induce various tumor types, and immunocompetence. On the other hand, this model often shows a different response in comparison to the results from in vitro assays in human cancer cells. To overcome this disadvantage, the National Cancer Institute (NCI) used a method in which human cancer cells are injected into an immune-deficient mouse. A battery of xenograft models was developed from eight different NCI cancer cell lines (brain, colon, leukemia, lung, melanoma, ovarian, prostate and renal). In addition, various methods for generating mouse models have been established for the assessment of the efficacy and toxicity of new drugs. One model is the genetically engineered mouse model (GEMM), which is an advanced method for evaluating carcinogenesis mechanisms and drug resistance (4). Immunocompetent mice are used for the GEMM model, similar to a syngenic model. So, this model allows the application of immune adjuvant development for cancer. Moreover, this model is useful for elucidating biological processes and investigating tumor cells and their microenvironment, but it is very expensive, heterogeneous and complicated. Additionally, tumor frequency, development and growth do not coincide in the GEMM model . Many researchers have devised a strategy for preclinical evaluation to determine the therapeutic potential and to mimic the human tumor environment. In addition to the GEMM model, in vivo xenograft models use athymic nude mice and severe combined immune deficiency (SCID) mice for implantation of the human cancer cells or patient tumor tissue in translational research for clinical trials. In this review, the types and characteristics of the tumor xenograft models are focused towards use in the development of anticancer drugs.