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Humanized Mouse and Rat PDX Cancer Models

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Patient-Derived Xenograft Models of Human Cancer

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Abstract

Oncology drug and therapeutic developments are hindered by lack of appropriate preclinical models that faithfully recapitulate tumor pathology, tumor growth and metastasis, genetics, and the tumor microenvironment. In particular, in vitro modeling of tumors often results in a cell line that differs from the patient’s tumor in key genetic aspects directly relating to the cancer phenotype and which thus differs in response to various treatments. Immunodeficient mice have paved the way for in vivo modeling of tumors and disseminated cancers. Growth kinetics and response to therapeutics can be more appropriately modeled in these systems. In addition, the advent of patient-derived xenografts (PDXs), whereby a piece of tumor is taken directly from the patient and grown in the mouse, demonstrates that personalized cancer treatments could be the standard of care. Recent advances in genetically modified rats provide another platform for modeling human cancer and PDX tissues. The rat offers a number of advantages over the mouse, including easier surgical manipulation, larger tumor size and greater blood volume for downstream analyses, as well as being the preferred model for drug efficacy and toxicology studies. This chapter reviews advances in human PDX modeling in the mouse and rat.

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Abbreviations

FSG:

F344-scid gamma

GFP:

Green fluorescent protein

NK:

Natural killer

NOD:

Nonobese diabetic

NSG:

NOD scid gamma

PDTX:

Patient-derived tumor xenograft

PDX:

Patient-derived xenograft

SCID:

Severe combined immunodeficiency

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Noto, F.K., Yeshi, T. (2017). Humanized Mouse and Rat PDX Cancer Models. In: Wang, Y., Lin, D., Gout, P. (eds) Patient-Derived Xenograft Models of Human Cancer . Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-55825-7_4

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