What Does the Prostate’s Very Early Development Have To
  Do With Advanced Cancer?


Edward M. Schaeffer, M.D., Ph.D., the Virginia and Warren Schwerin Scholar, has made great strides in understanding how the prostate develops, how hormones affect this, and how what happens before a man is even born has a lot to do with the most dangerous
kind of prostate cancer.

In extensive work with pathologist David Berman, M.D., Ph.D., and others, Schaeffer has figured out how male hormones, called androgens, make the prostate develop. He helped create a painstaking roadmap to chart all the genes that get turned on as the prostate grows explosively, turning from a tiny bud into an organ. This same program of growth, he and Berman have found, is reactivated in prostate cancer — especially when the cancers morph into more advanced and invasive types. It’s deja vu of the worst kind: “In many ways,” he says, “it’s like a reversion to an earlier state.”

If you’ve ever seen time-elapsed photography,you can imagine what it’s like for scientists watching the progress in an embryo. With remarkable speed, the embryo does its job — moving from one cell to a few primitive tissues, to forming organs. In the developing prostate, this rapid growth is driven and regulated by androgens; this happens in cancer, too — particularly in the most aggressive and malignant tumors. In their research, recently published in the journal, Oncogene, Schaeffer and Berman also discovered that some other genes, previously unrecognized, are turned on in both processes,as well. One gene, the transcription factor Sox9, causes growth in the developing prostate, and is expressed abnormally in early prostate cancers.

Instead of reinventing the wheel, prostate cancer is grimly practical; it just recycles.

Another, called Annexin A1, prevents cells from dying — which all cells, normally, are supposed to do.“These results help us understand better how prostate cancers develop,” says Schaeffer. “Prostate cancer is not a random process.” Instead of “reinventing the wheel,” prostate cancer is grimly practical; it just recycles. “It uses many of the same aggressive growth programs from development.” The big difference however, is that one process is not fatal. “The growth programs that stop in development keep going in cancer. Our next key step will be deciphering ways to turn these processes off in cancer.”

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