Assessing therapy response in patient-derived xenografts

Sci Transl Med. 2021 Nov 17;13(620):eabf4969. doi: 10.1126/scitranslmed.abf4969. Epub 2021 Nov 17.


Quantifying response to drug treatment in mouse models of human cancer is important for treatment development and assignment, yet remains a challenging task. To be able to translate the results of the experiments more readily, a preferred measure to quantify this response should take into account more of the available experimental data, including both tumor size over time and the variation among replicates. We propose a theoretically grounded measure, KuLGaP, to compute the difference between the treatment and control arms. We test and compare KuLGaP to four widely used response measures using 329 patient-derived xenograft (PDX) models. Our results show that KuLGaP is more selective than currently existing measures, reduces the risk of false-positive calls, and improves translation of the laboratory results to clinical practice. We also show that outcomes of human treatment better align with the results of the KuLGaP measure than other response measures. KuLGaP has the potential to become a measure of choice for quantifying drug treatment in mouse models as it can be easily used via the website.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Heterografts*
  • Humans
  • Mice
  • Xenograft Model Antitumor Assays