Abstract

The use of patient-derived xenografts (PDXs) has dramatically improved drug development programs. PDXs (1) reproduce the pathological features and the genomic profile of the parental tumors more precisely than other preclinical models, and (2) more faithfully predict therapy response. However, PDXs have limitations. These include the inability to completely capture tumor heterogeneity and the role of the immune system, the low engraftment efficiency of certain tumor types, and the consequences of the human-host interactions. Recently, the use of novel mouse strains and specialized engraftment techniques has enabled the generation of "humanized" PDXs, partially overcoming such limitations. Importantly, establishing, characterizing, and maintaining PDXs is costly and requires a significant regulatory, administrative, clinical, and laboratory infrastructure. In this review, we will retrace the historical milestones that led to the implementation of PDXs for cancer research, review the most recent innovations in the field, and discuss future avenues to tackle deficiencies that still exist.

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