Study Links Gene with Aggressive Prostate Cancer

A team of Harvard researchers recently identified a gene that may play a direct role in developing aggressive prostate cancer—a discovery they said could lead to a more accurate technique to test for the disease.

The researchers told The Crimson yesterday that the gene DAB2IP has the potential to serve as a better marker for doctors to predict prostate cancer’s progression, which could translate into more appropriate treatments.

“Though other genes in this pathway have been shown to correlate with [advanced prostate cancer], this gene goes one step farther,” said Harvard Medical School Assistant Professor Karen M. Cichowski, who led the study. Cichowski said the gene DAB2IP plays a direct role in causing prostate cancer to spread.

The study—published Sunday in the journal Nature Medicine—found a strong correlation between lacking the gene DAB2IP and a higher chance of developing prostate cancer in mice. The scientists’ findings were corroborated when they analyzed the tissue samples of hundreds of prostate cancer patients.

The researchers also identified the pathway causing prostate cancer to metastasize—which involves a protein coded by the gene EZH2. Loss of DAB2IP “liberates” EZH2 to drive downstream metastatic genes, researchers said.

“Understanding how this gene [DAB2IP] regulates metastasis at a deeper level...can ultimately lead to a new step in understanding not just prostate cancer, but how metastasis occurs,” said HMS Professor William C. Hahn ’87, an author of the paper.

Prostate cancer, which affects one in six men, is one of the leading causes of death for men in America, according to the Prostate Cancer Foundation. If detected early, the cancer is curable, but in its advanced stage it is not.

Early stage prostate cancer can be harmless, and might never present health problems even if untreated. But in some patients, the cancer metastasizes, spreading to other parts of the body and becoming more dangerous.

According to the researchers, doctors cannot accurately predict if a patient’s tumor will remain benign or spread to other tissues.

“There’s a potential problem with both under-treating and over-treating,” Cichowski said.

“You don’t want to do a life-altering procedure if the patient’s cancer would have never progressed,” she added. “At the same time, you don’t want a patient to develop a malignant tumor and die if we could have simply treated [it] more aggressively.”

Both Hahn and Cichowski said they believe that the gene DAB2IP could be an answer to this problem, adding that they hope to see more research devoted to studying the pathway.

—Staff writer Helen X. Yang can be reached at hxyang@fas.harvard.edu.

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