Single mouse testing may be an efficient approach to assess cancer therapies in children. In a prospective study, researchers established that single mouse models provided results similar to conventional testing, saving resources to study more tumor types.

Single mouse testing may be an efficient approach for assessing pediatric cancer therapies, according to findings presented at the 2020 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, held virtually October 24–25. In a prospective study, researchers in the Pediatric Preclinical Testing Consortium established that the method yields results similar to conventional testing, saving resources to study more tumor types.


Drug development for pediatric cancers has been slow, in part because such malignancies are rare and about 80% of children are cured by standard therapies—leaving few patients eligible for clinical trials. “Less than 30% of drugs tested in adults are tested in childhood cancer patients,” said Peter Houghton, PhD, of the Greehey Children's Cancer Research Institute in San Antonio, TX, who presented the results. Thus, better drug-testing strategies are needed.

Enter single mouse testing, which involves creating a patient-derived xenograft—grafting a patient's tumor sample into an immune-deficient animal to see how it responds. Researchers hypothesized that one animal would be sufficient to model a tumor from an individual patient, whereas conventional testing requires eight to 10 mice per tumor model. In a retrospective study assessing 67 drugs in 21,134 drug–tumor combinations, single mouse testing matched conventional methods for predicting drug responses in 78% of experiments (Cancer Res 2016;76:5798–809).

Those findings led Houghton and his team to conduct a prospective study comparing single mouse and conventional testing of topotecan, birinapant (TL32711; Medivir), and eltanexor (KTP-8602; Karyopharm Therapeutics) in leukemias, and trastuzumab deruxtecan (Enhertu; AstraZeneca/Daiichi Sankyo) and the antibody–drug conjugate mCD276-PBD in solid tumors. In both situations, single mouse testing agreed with conventional testing at least 80% of the time—and could analyze more tumor types. Additionally, single mouse models could determine whether tumors had poor, intermediate, or exceptional sensitivity to drugs.

“The single mouse testing method allows for far greater genetic and epigenetic diversity to be incorporated into preclinical testing,” Houghton said, estimating that 5,446 mice would be required for conventional testing, compared with 315 single mouse models used in the study, to capture the same information. “I think this is going to dramatically advance how we can screen drugs, and move drugs into the clinic much, much faster,” he concluded—a needed improvement because the Research to Accelerate Cures and Equity for Children Act requires increased testing of cancer drugs.

“Oncology approval rates are still low despite the fact that we know so much more about cancer as a disease,” said Bill Sellers, MD, of the Broad Institute of MIT and Harvard in Cambridge, MA, who provided commentary. “And [they're] low because we often don't do the extensive modeling to make better predictions about who to enroll on the trial.”

“I really love the efficiency of the single mice model study because that does really allow for quicker analysis of multiple models,” added James Gulley, MD, PhD, of the NCI, who also offered commentary.

Another benefit of single mouse testing is that it is much closer in design to an early clinical trial than a conventional preclinical study, said Stefan Pfister, MD, of the German Cancer Research Center and Hopp Children's Cancer Center in Heidelberg, who is involved in Europe's similar Paediatric Preclinical Proof of Concept Platform. Single mouse models “will, in my opinion, be a very important factor to increase the predictivity of preclinical testing,” he added—and developing them “should almost be a no-brainer.” –Catherine Caruso

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