The mice with human tumours: Growing pains for a popular cancer model

Cassandra Willyard in Nature:

Lindsey Abel takes an anaesthetized mouse from a plastic container and lays it on the lab bench. With a syringe, she injects a slurry of pink cancer cells under the skin of the animal’s right flank. These cells once belonged to a person with tongue cancer, a former smoker whose disease recurred despite radiation and surgery. The mouse is the second rodent to harbour them, creating a model for cancer known as a patient-derived xenograft (PDX). The tumour that grows inside will provide cells that can be transferred to more mice. Abel has performed this procedure hundreds of time since she joined Randall Kimple’s lab at the University of Wisconsin–Madison. Kimple, a radiation oncologist, uses PDX mice to carry out experiments on human tumours that would be impractical in people, such as testing new drugs and identifying factors that predict a good response to treatment. His lab has created more than 50 PDX mice since 2011. Kimple’s lab is not the only one doing this; PDX mice have exploded in popularity over the past decade and are beginning to supplant other techniques for modelling cancer in research and drug development, such as mice implanted with cancer cell lines. Because the models use fresh human tumour fragments rather than cells grown in a Petri dish, researchers have long hoped that PDXs would model tumour behaviour more accurately, and perhaps even help to guide treatment decisions for patients. They also allow researchers to explore the vast variety of human tumours. PDXFinder, a catalogue launched earlier this year, lists more than 1,900 types of PDX mouse. But there are many more scurrying around in academic and industry labs — as many as 10,000 PDXs have been created, says Nathalie Conte, a bioinformatician at the European Bioinformatics Institute, in Hinxton, UK, who leads PDXFinder.

PDX models are not perfect, however — and scientists are beginning to recognize their shortcomings and complexities. The tumours can diverge from the original sample, for example, and the models cannot be used to test immunotherapies. Now, biologists are scrutinizing PDX mice and looking for creative ways to cope with the challenges. “Every model is artificial in some way,” says Jeffrey Moscow, head of the investigational drug branch at the National Cancer Institute in Bethesda, Maryland. “The real question is how predictive are these models going to turn out to be.”

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