Blood cancers

‘Mouse avatar’ xenografts accepted to guide choice of cancer treatment

The use of patient-derived xenografts in ‘mouse avatars’ is a highly acceptable approach to guide the choice of cancer treatments, Australian research shows.

According to a survey of 1,550 cancer survivors, parents of childhood cancer survivors and people unaffected by cancer, the potential advantages for personalised cancer care far outweigh the disadvantages.

The findings were presented recently at the Precision Medicine in Paediatric Oncology meeting in Toronto and published in EBioMedicine.

Participants were presented with hypothetical questions about whether they would be willing to use patient-derived xenografts after a cancer diagnosis, how much they would pay, how long they would wait for results and the acceptable number of mice to be used.

The study found more than 80% of participants who had been affected by cancer were willing to use patient-derived xenografts compared to 68% of other participants.

The main driver for willingness to use xenografts was an ‘increased chance of survival’ – above other possible advantages such as faster recovery and avoiding other drugs.

Participants with an experience of cancer were prepared to pay more for patient-derived xenografts, wait longer and use more mice than other participants.

Parents of childhood cancer survivors were particularly willing to use the xenografts, with 38% prepared to pay the maximum proposed amount of $50,000.

And the use of experimental animals was a small consideration for parents with the majority (59%) willing to use up to 1,000 mice for testing.

The willingness to use patient-derived xenografts was largely similar amongst cancer survivors irrespective of their type of cancer.

Professor Claire Wakefield, from the University of NSW and Kids Cancer Centre at the Sydney Children’s Hospital, told the limbic patient-derived xenografts were already one of the testing platforms used in children with high-risk cancer as part of the Zero Childhood Cancer program.

“It is in clinical trials now. We’ve already had over 100 kids go through the Zero program and they are actually feeding the results back to their physicians if they are successful.”

“Mostly the program does a very large drug screen in vitro first and then tests the best possible candidates in a cohort of mice.”

Given the time required for the xenografts to grow, results can take 4-6 months so patients are initially treated on the basis of standard genetic and in vitro test results.

“The doctor may use the results then as back up if the child’s initial treatment isn’t working or the cancer comes back.”

Professor Wakefield said the issue of using mice in the context of patient-derived xenografts was confronting for some people but typically overridden by personal experience of cancer.

“Everybody knows theoretically that all of the medications they take have been tested on animals in the past, but this is really different because it is a more direct link to current animals. It’s quite different to knowing that the chemo you have was tested on animals 15-20 years ago.”

She highlighted a powerful piece of writing from a young cancer patient grappling with the relationship between him and the animals.

Professor Wakefield added it will be interesting to re-do the acceptability survey when more is known about the efficacy of patient-derived xenografts.

“We were pretty clear to our participants that we don’t know if it going to be effective or not. It sounds plausible and appealing, just like the whole precision medicine concept. But if we re-did it in five years and were able to say it improved people’s chance of survival then I think you would get a swing to even higher acceptability.”

“But vice versa, if we were at that point with five years research and haven’t shown very clear improvement then you might find more people being a little bit more cautious about it, particularly around paying.”

A prospective study of attitudes to xenografts is currently underway as part of the Zero Childhood Cancer program.

“My suspicion is it will be even more acceptable when you are facing a current cancer threat but there might also be some unrealistic expectations around what it can offer and potentially some disappointments when the models don’t identify any new potential treatments.”

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