Of mice and men

Men with prostate cancer now find hope in a mouse hospital in Boston

Written by Gina Kolata | Boston | Published: June 16, 2013 12:52:36 am

At Beth Israel Deaconess Medical Centre,a black mouse lies on a miniature exam table,his tail dangling off the end. A plastic tube carries anesthetic to his nose and mouth. He is asleep.

Before he was born,the mouse was injected with two mutated genes often found in human prostate cancer. As he lies on the table,a technician is measuring his 2-mm prostate tumour with an ultrasound machine—the very exam a man would undergo,only on a dollhouse scale.

The animal is in what is called a “mouse hospital,” a new way of using mice to study cancer. The hospital at Beth Israel Deaconess is at the forefront of a new approach to studying human cancers. The mice are given genes that make them develop tumours in the same organs as humans. What’s more,with genetic advances in studies of human tumours,the researchers do not have to implant human cancer cells into mice to study the cancers; instead,they can give the mice just a few mutated genes that seem to drive a tumour.

They genetically alter the mice before they are born and then,with scanners,watch what happens as a cancer develops in the expected organ—the prostate,in this case. Then they can try out drugs designed to attack those gene mutations and the cancers they cause.

The result,so far,has been astonishing. The mice with just a few cancer genes developed prostate cancer when they grew up. The cancer responded to the standard treatment—castration or,in the case of patients,chemical castration. Because so few genes were involved in the mouse prostate cancer,the investigators,including Andrea Lunardi of Beth Israel Deaconess,could pinpoint the genetic roots of the treatment resistance.

The solution seems obvious,said Dr Pier Paolo Pandolfi,scientific director at Beth Israel Deaconess Medical Centre. By making mice with only one or a few suspect mutations at a time,scientists cut through the chaotic

genetic noise.

The investigators just started one clinical trial to see if the mouse studies predict what will happen in patients and are about to start another.

Don De Grandis is patient No. 1 in the first study. He found that he had prostate cancer when what he thought was a muscle pull turned out to be bone pain from a cancer that had already spread to his bone marrow. The cancer was too advanced to cure,and the standard testosterone-blocking drug had stopped working.

So far,some of the mouse proxies getting the same drugs as De Grandis are responding too. The cancer progresses much faster in mice,so the animals might give a foretaste of what is to come in the men to whom they are matched.


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