Improved drug-screening tests of candidate anti-cancer drugs in patient-derived xenografts through use of numerous measures of tumor growth determined in multiple independent laboratories
Elizabeth Rosenzweig, David E. Axelrod, Derek Gordon
Abstract
Background
Researchers screen candidate anti-cancer drugs for their ability to inhibit tumor growth in patient-derived xenografts (PDXs). Typically, a single laboratory will use a single measure of tumor growth.
Introduction
We develop methods for evaluating the results of preclinical drug-screening tests. We compare several different measures of drug inhibition of tumor growth in patient-derived xenografts (PDX), and evaluate the benefit of determining inhibition in different laboratories. The criteria of sensitivity, specificity, and accuracy determine the best experimental design and statistical analysis. The significance of this work is that more accurate drug-screening tests improve decision-making in selecting effective cancer treatments.
Materials and method
Ethics statement on human participants
None of the data used in this study came from human participants. No ethics committee approval was necessary because we did not conduct animal studies, nor did we use data from prospective or retrospective human research studies.
Results
Drug screening tests for candidate anti-cancer drugs from a single laboratory may include multiple drugs and multiple tumors [5]. The reproducibility of drug screening tests can be determined by comparing the results of multiple statistical tests from numerous laboratories that treat the same tumors with the same drugs [2]. We perform these comparisons in the work that follows. The term precision refers to the length of the 95% confidence interval. The smaller the length, the greater the precision, and vice versa. Also, in all sections that follow, we employ the notation from Table 3, M = 5, L = 5 (Fig 2, Step 8).
Discussion
We have shown in this paper that drug screening tests that incorporate numerous tumor growth measures and meta-analysis across numerous independent experiments are equivalent to or an improvement on the Single-Measure, Single-Lab screening test in terms of sensitivity, specificity, and accuracy. We therefore recommend using multiple tumor growth measures and multiple experiments when evaluating candidate cancer drug effectiveness in PDX trials.
Acknowledgments
The authors thank Michael Lloyd for furnishing patient-derived xenograft data used in the manuscript “Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis” authored in 2020 by Evrard et al. We additionally acknowledge the authors of “High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response” authored in 2015 by Gao et al., for providing their patient-derived xenograft data freely as a supplement to their publication.
Citation: Rosenzweig E, Axelrod DE, Gordon D (2025) Improved drug-screening tests of candidate anti-cancer drugs in patient-derived xenografts through use of numerous measures of tumor growth determined in multiple independent laboratories. PLoS One 20(6): e0324141. https://doi.org/10.1371/journal.pone.0324141
Editor: Afzal Basha Shaik, Vignan Pharmacy College, INDIA
Received: November 18, 2024; Accepted: April 21, 2025; Published: June 18, 2025
Copyright: © 2025 Rosenzweig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
