Animal Rights

More Mouse Models of Cancer, Still Not Human

| by Dr Ray Greek

There have been many attempts to reproduce human cancers in mice. The nude mouse lacked the FOX1 gene, the SCID mouse was created with a very deficient immune system, and there have been many more. All have failed to predict human response and have misled researchers. When I say things like that, the vested interest groups go wild accusing me a of being an antiscience, misanthropic, lunatic, animal rights activist.

In the April 1, 2010 issue of The Scientist some scientists apparently missed the memo warning them not to agree with me. The article is about yet another effort to make mice into humans. But interestingly, the article says:

Most of the time, in order to test a cancer therapy, researchers simply transplant human cancer tissue into a mouse. But those experiments rarely predict how a human will respond to the same treatment . . . Mouse models that use transplants of human cancer have not had a great track record of predicting human responses to treatment in the clinic. It’s been estimated that cancer drugs that enter clinical testing have a 95 percent rate of failing to make it to market, in comparison to the 89 percent failure rate for all therapies . . . Indeed, we had loads of models that were not predictive, that were [in fact] seriously misleading,” says NCI’s Marks, also head of the Mouse Models of Human Cancers Consortium, a network of cancer researchers (including Pandolfi) who set goals, meet regularly, and collaborate in their search for a better mouse model. In 2001, researchers at the NCI looked at the xenograft data from 39 cancer drugs that had already successfully completed Phase II trials in humans. Only one of the xenograft models showed a similar response to the cancer drug as the patients who received it (Br J Cancer, 84:1424–31, 2001) . . . Scientists and companies compound the problem by putting too much stock in the results from these troubled models. [1] (Emphasis added.)

Historically researchers who use mice have defended the practice saying the mouse models were invaluable for informing about the human disease. I guess they were engaging in a bit of irrational exuberance there. No matter. Now they are saying the new mouse models will be great. Of course, not everyone is saying that:

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The National Cancer Institute awarded the trial more than $4 million in stimulus funds, but Cheryl Marks, the director of the NCI’s division of cancer biology, isn’t entirely convinced that these [new] genetically modified mice will prove more predictive than the standard human transplant model. “This [trial] is the first thing that would make a believer out of you,” she says. “To me, the jury is out” . . . But will this model, or any other, predict human experiences of toxicity, recurrence, drug response, metastasis? “It’s a very challenging question,” says Marks. [1]

At some point society must hold responsible the researchers whose failures cost precious money that could have gone into studying humans with cancer. These scientists told society cures were coming from the mouse models and that the mouse models could predict human response. Likewise, society must also call into question current claims being made by essentially the same people.

Instead of using mice, scientists could study humans with cancer and the cancerous tissues from those humans. What a novel idea; study the species you want to cure. But until society realizes lives are being lost and demands an end to white coat welfare, the status quo is unlikely to change.

(For more in cancer and animal models see Animal Models in Light of Evolution.)

References

1. Zielinska E: Building a better mouse. The Scientist 2010, 24:34-38.