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Genetic Markers Are Key For Prostate Cancer Treatment - 2001-08-23

U.S. researchers have come up with a list of genetic markers for prostate cancer that will help doctors determine how serious a man's case is and how aggressively to treat it. This so-called molecular profiling is a promising new technique that is finding its way into assessments of other types of cancers.

In any detective work, the more clues, the better. When doctors want to know if a man has cancer of the prostate gland, they measure blood levels of a chemical called prostate specific antigen, abbreviated PSA. But an elevated PSA level is not a perfect clue because it can be high in non-malignant conditions.

Tissue samples offer a much better chance of detecting prostate cancer. But if a tumor is found, not all are equally virulent or require the same therapy.

How is a doctor to know? A new study in the journal Nature shows the way.

University of Michigan Medical School researchers led by physician Arul Chinnaiyan compared several hundred samples of normal and malignant prostate tissue to see what genes were more common in the malignancies. They did this by using a relatively recent technological advance that allows scientists to gather many genes together on so-called "DNA chips."

"We describe in our study that we found about 200 or so genes out of approximately 10,000 that we were looking at that correlated with some form of prostate cancer, either increased or decreased prostate cancer," says Dr. Chinnaiyan.

Many of the genes had already been linked to cancer, but others were not until this study.

Dr. Chinnaiyan and his colleagues say the result of their work is a select set of genes that define a molecular signature for prostate cancer. If any combination is found in a prostate tumor sample, they could alert a physician to the status of the cancer.

"We can definitely under the microscope," notes Dr. Chinnaiyan. "A pathologist can tell you whether a patient has cancer or not. However, these sorts of markers are going to supplement even what a pathologist sees, in that it may add information as to the aggressiveness of a particular patient's cancer and whether it really needs to be treated or can just be watched."

Other studies must confirm these results. A further step is defining the proteins that the prostate cancer genes produce. The Michigan researchers traced proteins from two genes as case studies.

According to U.S. Food and Drug Administration scientist Emmanuel Petricoin, the ability to tailor treatments to the individual patient depends on developing drugs that target specific cancer proteins in the patient's tumor.

"In the future, as we gain more and more of these expressed proteins, we will be able to more further refine the analysis and really come up with specific portraits that will help predict outcomes or will give clues to specific treatment strategies," says Mr. Petricoin.

The University of Michigan gene study applied a technique researchers have used for other forms of cancer in the past few years.

National Cancer Institute physician Lance Liotta says this kind of tumor analysis is the future of cancer therapy. He says the institute is carrying it even further by also looking for pathways by which cancer's chemical signals are sent.

"Then we would specifically tailor therapies to the individual deranged signaling pathway in that person's cancer," adds Dr. Liotta. "So we would have tailored therapies that have a greater chance of being effective, have lower toxicity, and have a greater chance of resisting the tumor growing back."

Dr. Liotta says the work could lead to combinations of drugs for combinations of proteins and provide more complete therapy than a single drug for one protein, which might develop resistance to the compound.