In a recent episode of Freakonomics Radio, the hosts asked guests to identify ideas “we cling to” that might actually impede progress. Oncologist Azra Raza points to the futility of using mouse models for human cancer research. In the podcast, Dr. Raza’s segment begins at 00:15:10, and ends at 00:19:31. Here is a transcript of her comments:
My name is Azra Raza. I am an oncologist, professor of medicine and director of the MDS Center at Columbia University in New York. The scientific idea that I believe is ready for retirement is “mouse models” must be retired from use in drug development for cancer therapy because what you see in a mouse is not necessarily what you are going to see in humans. For example, one very simple mouse model would be we take a mouse and give it a drug and see what happens to it. Another, which is much more commonly used, is called xenograft mouse model in which what we do is that we will take a mouse and we will use radiation therapy etcetera to destroy its immune system completely. And now we will transplant a tumor taken from a human into this mouse model. So its own immune system is gone, so it won’t reject the tumor, and we can then test the efficacy of a drug to kill these human cells in the xenografted mouse model. Now, currently cancer affects one in two men and one in three women. It’s obvious that despite concerted efforts of thousands of investigators, cancer therapy is today like beating a dog with a stick to get rid of its fleas. It’s really, in general, quite primitive. In fact, the acute myeloid leukemia – the disease I’ve been studying – we are giving the same drugs today for the majority of patients that we were giving in 1977 when I started my research in this area. So when compared to let’s say things like infectious diseases or cardiac drugs, cancer drugs fail more often. Recently things have improved. From the mid-90s to now, about 20% of drugs are actually entering clinical trials and FDA approved. But 90% of the drugs still fail because of either unacceptable toxicity, or once we give them to humans we find that they’re not working the way they were supposed to. So why are these facts so grim? Because we have used a mouse model that is misleading. They do not mimic human disease well and they’re essentially worthless for drug development. It’s very clear that if we are to improve cancer therapy we have to study human cancer cells. But in my opinion too many eminent laboratories and illustrious researchers have devoted entire lives to studying malignant diseases in mouse models. And they are the ones reviewing each others’ grants and deciding where money gets spent. So they’re not prepared to accept that mouse models are basically valueless for most of cancer therapeutics. But persisting with mouse models and trying to treat all cancers in this exceedingly artificial system will be a real drawback to proceeding with personalized care based on a patient’s own specific tumor, its genetic characteristics, its expression profile, its metabolomics; all those things are so individually determined in cancer. And for a lot of patients the drugs are already there we just have to know how to match the right drug to the right patient at the right time, and in order to do that the answer is not going to come from mouse models, but its is going to come from studying human cancers directly. Mice just are not men.