Identifying Aggressive Prostate Cancers

Roswell researchers developing genetic testing to establish if prostate cancer is slow-growing or fast-growing. Test to help patients, doctors to determine cancer treatment

By Deborah Jeanne Sergeant

Prostate cancer is one tricky cancer.

Men with prostate cancer may have a tumor that doesn’t grow or spread quickly. In this case, a wait-and-see option may be favorable over prostatectomy, which can cause side effects like incontinence and impotence.

But other men have aggressive tumors that spread to other areas of the body rapidly. Surgery or follow-up cancer treatments can give them the best chance to save their lives.

Telling the difference between slow-growing and fast-growing and recurring tumors has relied mostly on prostate-specific antigen (PSA) testing. But soon, genetic testing may lend a hand.

Factors other than prostate cancer can elevate the PSA level. Obesity and other factors can abnormally lower PSA levels. Various factors can skew PSA testing, resulting in false negatives or false positives.

Researchers with Roswell Park Cancer Institute in Buffalo, led by Irwin H. Gelman, Ph.D., have identified the 11-gene signature linked to advanced, recurrent prostate cancer. Once they establish the gene signature’s predictive value, they can perform a biopsy to give men and their doctors more information to make what is often a life-altering decision.

Gelman directs Research Integration and serves as a distinguished professor of oncology, along with chairing the Cell & Molecular Biology academic program. He also directs shRNA Core Resource at Roswell Park Cancer Institute.

“The signature is based upon trying to predict early on whose cancer might recur,” Gelman said. “The research is to look at tumors, or human cell lines which recapitulate this recurrence type of disease and then trying to find out genetic gene signatures that align with a recurrence versus a primary disease.”

Men with family history of prostate cancer are more likely to have a more aggressive prostate cancer, which makes such testing even more meaningful.

Gelman and his team hope to start a clinical trial to confirm that the gene signature can accurately predict which tumors will spread and recur and which ones won’t. For those with recurring tumors, treating with drugs that attack the gene signature can disrupt the cancer’s mechanism and “decrease significantly the recurrence of the disease,” Gelman said.

“Hopefully, it will become a predictive marker to figure out who’s at higher risk and develop and test to decrease the incidences of occurrence.”

The team has a few ideas of drugs that could be useful in preventing recurring prostate cancer, and hope to complete a trial in a few years.

William Phelps, PhD, works with American Cancer Society-funded researchers as vice president of Extramural Research in Atlanta, Ga.

He said that the question of whether a tumor is slow growing or fast growing “is certainly one of the critical questions that physicians don’t have a tool to answer.

“People’s perception of cancer can be, ‘Just get it out of me.’ But if they want to wait and see, it is absolutely a critical question if their cancer will grow quickly and the field needs this as a prognostic and diagnostic tool.”

David Albala, chief of urology at Crouse Hospital and a partner at Associated Medical Professionals of NY, compared identifying aggressive prostate cancer with genetic testing to determining risk of breast cancer.

“Currently, there are a number of commercially available genetic profile tests to help us make decisions in prostate cancer,” Albala said. “Many with low-risk prostate cancers, we can do active surveillance on.”

“If the risk was high you might want to look at other treatment. Co- morbidity and age play into it.”

For example, a tumor that’s growing slowly in a man who’s 89 and has experienced two strokes is treated much differently than a slow-growing tumor in a man who’s 50 and in otherwise good health.

“I think the future is in the next type of marker, phenotypic marker,” Albala said. “Understanding genomic markers is like taking a picture of a certain number of genes and understand how they related to prostate cancers. It’s how the tumor reacts in the environment. We’ve been doing cutting-edge research.”

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