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Missing gene tied to lethal prostate cancer

Leszek Kotula, MD, PhD, associate professor of urology and molecular biology, in his Upstate laboratory. (PHOTO BY WILLIAM MUELLER)

Leszek Kotula, MD, PhD, associate professor of urology and molecular biology, in his Upstate laboratory. (PHOTO BY WILLIAM MUELLER)

Men diagnosed with prostate cancer who lack a particular gene called WAVE-1 may have better survival odds if they are treated early.

That‘s according to research from scientists at Upstate Medical and Harvard universities, who worked together to link the absence of a WAVE-1 gene to a lethal form of prostate cancer. Their research – based on analysis of public databases – was published in March in the journal Oncotarget.

“We observed that prostate cancer tumors contain a frequent deletion of the WAVE-1 gene. What‘s important, though, is that this WAVE-1 gene deletion occurs in metastatic and lethal cancer, thus suggesting that the WAVE-1 gene loss may represent an aggressive subtype of prostate cancer which is more challenging to treat and more likely to progress,” said study co-author Leszek Kotula, MD, PhD, associate professor of urology and biochemistry and molecular biology at Upstate.

“It is possible that patients who have tumors characterized by the deletion of the WAVE-1 gene may benefit from earlier intervention, such as surgery or radiation therapy,” he said.

The researchers found that alterations in the WAVE-1 gene were associated with a shorter period of remission in patients who were treated for prostate cancer. They also discovered that almost a quarter of the prostate cancers reviewed in the database lacked the WAVE-1 gene.

WAVE gene complexes are involved in cell motility and migration, cellular adhesion and cell-to-cell communications, numerous processes that can play a role in tumor progression and the spread of cancer.

“It is clear that disruption of the WAVE complex is associated with human cancers, including prostate cancer,” said Harvard‘s Adam G. Sowalsky, PhD, an instructor in medicine. He said further investigation is needed, but “because lethal prostate cancers show this disruption, we may be able to identify mechanisms that lead to the tumor cell acquiring resistance to advanced therapies.”

The study was paid for by the National Institutes of Health and the Department of Defense. Gennady Bratslavsky, MD, and MD/PhD student Rebecca Sager from Upstate were also involved in the work.

Kotula‘s previous research implicated a gene called ABI-1 as a tumor suppressor in prostate cancer. The Oncotarget study built on that, setting out to find other genes that cooperate with ABI-1 in the progression of prostate cancer. They found WAVE-1.

Now, Kotula‘s lab is replicating the WAVE-1 gene deletion in mice. Such work can aid in the development of drugs or new treatments to suppress tumors or provide more precision in the treatment of these aggressive cancers.

About prostate cancer

After skin cancer, prostate cancer is the most common cancer among men. About one man in seven will be diagnosed with prostate cancer during his lifetime. Most will not die from the disease, even though prostate cancer is the second leading cause of cancer death – behind lung cancer – for men.

 This article appears in the summer 2015 issue of Cancer Care magazine.