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Biomarkers May Be Key to Cancer Detection

But it's not yet clear which tests will be most useful, one expert says

WEDNESDAY, Sept. 13, 2006 (HealthDay News) -- Scientists have found a new batch of "biomarkers" that might someday be used to spot and predict the progression of prostate, colorectal and lung cancers.

"We are clearly moving to a better understanding of the genetics of cancer," said Dr. Len Lichtenfeld, the deputy chief medical officer at the American Cancer Society. "This change is evolutionary and revolutionary," he said.

The findings of five studies were presented Wednesday in Chicago at the first meeting of Molecular Diagnostics in Cancer Therapeutic Development, sponsored by the American Association for Cancer Research.

In the first report, German researchers found that two genes, REG1A and EXTL3, are "overexpressed" in colorectal cancer, meaning they produce so much of a protein that they can be harmful. In addition, REG1A was significantly overexpressed in biopsies taken from precancerous colon polyps, the researchers found.

"The findings suggest that the two genes are significant prognostic markers and may eventually help in making decisions about management of colorectal adenomas and tumors," lead researcher Wolfgang Kemmner, a surgical oncology research group leader at the Max Delbrueck Center, Berlin said in a prepared statement.

In the second report, researchers from Yale University School of Medicine showed that the levels of a protein called thymidylate synthase (TS) may be useful in predicting survival after colorectal cancer.

The researchers found that higher levels of TS in the cancer cell's nucleus were associated with lower survival time. In addition, the ratio of TS levels in the cell's nucleus compared to its cytoplasm also predicted survival, the researchers said.

"TS levels have been known as a marker for decreased survival and response to therapy, but this is the first study to show that the relationship between nuclear and cytoplasmic levels of TS can predict survival," researcher Mark D. Gustavson, a postdoctoral fellow in Yale's Department of Pathology, said in a prepared statement.

In the next study, researchers say a specific blood protein may help detect prostate cancer. They believe it may be a more accurate way of diagnosing the condition than current methods.

The protein is an enzyme called human aspartyl (asparaginyl) beta-hydroxylase, or HAAH. HAAH is overexpressed in at least 20 types of cancers tested to date, including liver, breast, ovarian, colon, esophageal, and prostate. It's also been shown to be involved in tumor growth, invasiveness and cancer spread, according to Dr. Stephen Keith, president and chief operating officer of Panacea Pharmaceuticals Inc., of Gaithersburg, Md. That company has developed a test to detect HAAH.

In experiments, the researchers found that men with prostate cancer had high HAAH levels, while men without the disease did not.

"We hope our HAAH blood test, combined with PSA and digital rectal examination, will increase the sensitivity and specificity of screening for prostate cancer," Keith said in a statement. "Those without cancer can avoid unnecessary biopsies through the use of all three screening tests," he added.

In the fourth study, researchers from Purdue University found a protein in the blood that they believe is a better indicator of prostate cancer's spread. The protein, called tNOX, is a member of a family of proteins involved in cell growth.

The researchers found that, based on PSA levels, prostate cancer that was continuing to grow had an average 60 percent higher level of tNOX compared with men whose cancer was stable.

"The more prostate cancer present as evidenced by PSA levels, the more tNOX protein that is present," lead researcher D. James Morre, a distinguished professor of medicinal chemistry at Purdue, said in a prepared statement.

In the last paper, another Purdue team said it has developed a test to detect lung cancer. This group, led by Dorothy M. Morre, a Purdue professor of foods and nutrition, also focused on tNOX. The researchers looked at tNOX levels in a group of patients with and without lung cancer.

"In healthy individuals, we have 0 out of 25 false-positives," Morre said in a prepared statement. "In lung cancers, 103 of the 104 patients were positive for tNOX. In smokers older than 40 years of age, 12 percent were positive, which is about the normal incidence picked up with high resolution tomography," she said.

Morre's team hopes that the tNOX test will be a screening tool for the early detection of lung cancer. People who test positive for tNOX would then have further tests.

It's still not clear if all or any of these biomarkers will make it all the way to a widely used test, Lichtenfeld said.

"Being able to sort all of this out to find which ones help and which ones are just 'of interest' is going to be a complicated and, perhaps, confusing process," he said. "Right now, it's all interesting. It's all exciting. But we have to be able to separate the background noise from the information that is really going to be helpful in diagnosing, monitoring cancer."

More information

There's more on cancer research at the U.S. National Cancer Institute.

SOURCES: Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; Sept. 13, 2006, presentations, Molecular Diagnostics in Cancer Therapeutic Development, American Association for Cancer Research meeting, Chicago
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