Primitive Pathways and Sophisticated Prostate Cancer

Pathologist David Berman, M.D., Ph.D., the R. Christian B. Evensen Scholar, seeking to stop prostate cancer at its most advanced and sophisticated, is looking at some of the body's simplest, most primitive devices. One of them, discussed in the last two issues of Discovery, is called the Hedgehog pathway — a common protein pathway that's involved in embryonic development of several organs, including the prostate.

Some of the gene functions
that happen early in development
are also very important in the
earliest beginnings of cancer.

But in prostate and other cancers, it turns out, this pathway serves as a lifeline that enables cancer cells to live and spread outside their original tumor. In exciting work, Berman and colleagues have proved that they can block this pathway, and stop cancer from spreading.

Now, in new research — the first of its kind — Berman is looking at another primitive structure called the urogenital sinus (UGS). Before birth, this structure, stimulated by testosterone, causes the prostate to grow. When this happens, there's also "a burst of proliferation, invasion of surrounding tissue by the growing cells, and the formation of new blood vessels," says Berman. "This is very similar to what happens in cancer." Could it be that learning how to control this process will help stop prostate cancer? In studies using mouse tissue performed with Brady urologist Ted Schaeffer, Berman has launched the first comprehensive analysis of gene activity in early prostate development. He and colleagues have identified several promising cellular pathways and signals that may control prostate growth.

Berman and bioinformatics experts Giovanni Parmigiani and Luigi Marchoni found that some of the gene functions most significantly associated with early prostate development are the ones in charge of cell proliferation, angiogenesis, and movement. Interestingly, these are all very important in early prostate cancer development, as well. Each cell in the body, Berman believes, has a different developmental history that restricts the genes it can activate later in life.

"Therefore, each category of cancer — such as prostate, breast, or colon — is likely to use a different assortment of genes and pathways to activate these processes." By identifying the molecular basis for these processes in prostate cells, Berman hopes his research will suggest new, more specific ways to treat prostate cancer while leaving the rest of the body unscathed.


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