November 24, 2014
 
prostate cancer discovery  
   THE BRADY UROLOGICAL INSTITUTE • JOHNS HOPKINS MEDICINE

   A PUBLICATION OF THE PATRICK C . WALSH PROSTATE CANCER RESEARCH FUND
   Volume VI, Winter 2011
 
   
 

Needed: A Better Animal Model for Aggressive Cancer

Alan Meeker
Meeker: Rats get more aggressive cancer.

When it comes to prostate cancer, men are much more like rats than mice. Rats, like men, spontaneously develop the disease. As it advances, the cancer changes in rats, as it does in men; it grows unstable and aggressive, becomes more likely to spread throughout the body, and to come back after treatment.

Although they’ve gathered many pieces of the puzzle, scientists still don’t know all the reasons why some men are fortunate enough to develop a mild, slow-growing form of prostate cancer, while others have the dangerous kind, the one that’s most likely to defy treatment. Identifying which type of cancer an individual patient has would help men and their doctors determine the best course of treatment.

One big roadblock in learning more about the complicated, advanced cancer that can so easily morph into different forms — each resistant and susceptible in its own way to various drugs designed to kill it — is the lack of a good animal model. Scientists trying to save the lives of men with prostate cancer have long studied the disease in mice, but there are limits, says Alan Meeker, Ph.D., the Virginia and Warren Schwerin Scholar. “None of the mouse forms satisfactorily mimics the most common lethal forms of metastatic human prostate cancer.” He believes this is because it takes several bad things happening in the genes — several different mutations — for the disease to progress in men, “but mouse models rely on the introduction of only one or two well-defined genetic changes.” Also, mouse models of cancer aren’t as unstable, and their disease tends to progress more slowly, or not at all.

On the other hand, rats — whose physiology more closely mimics human physiology than that of mice — have the potential to become excellent models of human prostate cancer, Meeker notes. However, at present “only one genetically engineered rat model exists, and this model is based on activating a protein that comes from a virus that has never been linked to human prostate cancer,” he adds. This rat model’s usefulness is limited, mainly because “it does not recapitulate important features of late-stage human prostate cancer.”

Meeker hopes to change this, by developing innovative models that more closely mimic key features of human prostate cancer. He is developing a rat model by recreating the same molecular changes that probably cause aggressive disease to begin and progress in men. The result of his work will not only help scientists learn more about the worst kind of prostate cancer, but will help them test new drugs aimed at these men who need it most.

Bottom Line:

Nearly all animal studies of prostate cancer are done in mice. Yet mice don’t develop the aggressive, unstable disease that causes such harm in men. Rats, on the other hand, like men, naturally develop the kind of prostate cancer that can be fatal. They have the potential to become excellent models of this disease, and to test new forms of treatment.

   


 

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