Patient-Derived Xenografts (PDXs) is a cancer model system that is presumed to faithfully represent the genomic features of primary tumors and as such is widely used by leading researchers in academia as well as in the pharmaceutical industry in drug discovery and development.
In an article published by researchers from the Broad Institute of MIT, Dana-Farber Cancer Institute and Harvard Medical School in Boston, geneticists monitored the dynamics of copy number alterations (CNAs) in 1,110 PDXs samples across 24 cancer types and presented findings that challenge PDX-based modeling of human cancer.
Specifically, the researchers observed rapid accumulation of CNAs during PDX passaging that differed from those acquired during tumor evolution in patients. In addition, several CNAs recurrently observed in primary tumors gradually disappeared in PDXs, indicating that events undergoing positive selection in humans can become dispensable during propagation in mice.
Finally, the authors noted that the genomic stability of PDXs was associated with their response to chemotherapy and targeted drugs, which together with the other finding, highlights the unmet needs still existing in personalized medicine and development of targeted therapies.
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