Beyond furry test tubes
High throughput screening of compounds in PDX models
In the largest study of patient-derived xenograft (PDX) mouse models published to date, researchers at Novartis Institutes for BioMedical Research (NIBR) have demonstrated that a high throughput preclinical trial for screening compounds in mice can faithfully reproduce the heterogeneity of responses observed in clinical trials, validate biomarkers and identify new mechanisms of drug resistance. The results are a departure from the spotty predictive value of standard models in oncology, and the team believes the experimental paradigm could increase clinical success rates by identifying the right patients to enroll in trials.
While conventional xenografts made from cell lines have been used for decades to screen compounds, companies have recently started turning to PDX models because they more closely mimic tumor biology in patients. However, PDX trials are mostly conducted on tumors derived from one or very few patients, limiting the chances of obtaining the diversity of responses seen in clinical populations...