How the Gordian Knot's Solution May Help Kill Prostate Cancer Cells

Remember the legend of the Gordian knot? It was so intricate that no one could figure out how to untie it, until one day Alexander the Great came to town and solved the problem his own way: He simply cut it with his sword. 

Michael Haffner, M.D., has discovered a similar story happening with hormones in prostate cancer. Male hormones, called androgens, help prostate cancer cells grow and survive using a complex network of chemical signals. "Recently we have uncovered a novel and striking aspect of androgen signaling,” says Haffner. It turns out that "these hormones can induce breaks in the DNA of prostate cancer cells. This hormonetriggered process is likely mediated by an enzyme called TO P2B, which can untangle knots in the DNA by simply cutting the DNA molecule.” Snip! and suddenly, it's a lot easier to undo one of these DNA snarls. In earlier work published in Nature Genetics Haffner, together with Srinivasan Yegnasubramanian, William Nelson and other Hopkins investigators found that activity of the TO P2B enzyme can lead to gene defects. Now "we have also uncovered that androgens can specifically induce DNA damage in prostate cancer cells,” Haffner adds. He and colleagues are investigating the biological role of androgen-induced breaks in the DNA "and more importantly, exploring the possibility of using these breaks to kill prostate cancer cells.” 

In laboratory experiments, the investigators are sending short pulses of androgens to induce DNA damage in prostate cancer cells. "Using this approach in combination with other treatments that block repair processes of androgen-induced DNA breaks, we hope to develop a highly specific therapy for advanced prostate cancer.” 

For his work on the role of androgeninduced DNA breaks in prostate cancer, Haffner has received the prestigious W. Barry Wood, Jr. Award, given to young investigators at Johns Hopkins for outstanding biomedical research. He also has received a Young Investigator Award from the Prostate Cancer Foundation.

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