Abstract
Patient-derived xenograft (PDX) mouse models of cancer were first established in 1969 and were very actively used in the 1970’s and 1980’s. After a long period of eclipse, PDX models began to re-emerge in the early part of the present century. PDX models have potential as an important component of personalized precision cancer therapy. However, most PDX models currently offered to patients have their tumors subcutaneously transplanted in immunodeficient mice, which rarely metastasize. In contrast, orthotopic-transplant patient-derived models, termed patient-derived orthotopic xenografts (PDOX), usually metastasize as in the patient. Orthotopic models are critically important for the patient, since both primary and metastatic tumors develop and they can have differential chemosensitivity, not detectable in subcutaneous tumor models. We review first studies of cancer cell lines which have different drug response patterns at the orthotopic and subcutaneous cites in mouse models. We then review a subcutaneous nude mouse model of patient HER-2 expressing cervical carcinoma that was not sensitive to entinostat (a benzamide histone deacetylase inhibitor). In the PDOX model, entinostat was not effective against the primary tumor. However, entinostat significantly reduced the metastatic tumor burden, compared to the primary tumor in the PDOX model. Thus, only the PDOX model could be used to discover the anti-metastatic activity of entinostat for this patient. We emphasize the importance of using mouse models that can accurately recapitulate metastatic cancer for precisely individualizing cancer therapy.
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Hoffman, R.M. (2017). Why Patient-Derived Mouse Models Need to Be Orthotopic. In: Hoffman, R. (eds) Patient-Derived Mouse Models of Cancer . Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-57424-0_20
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DOI: https://doi.org/10.1007/978-3-319-57424-0_20
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