The test, which zeroes in on a protein called human aspartyl (asparaginyl) beta-hydroxylase, or HAAH, appears to be more accurate than current methods for the early detection for prostate cancer, says Stephen Keith, M.D. Keith is president and chief operating officer of Panacea Pharmaceuticals, Inc., in Gaithersburg, Md., which is developing the new test.
About 234,000 Americans will be diagnosed with prostate cancer this year, and 27,000 men will die from the disease. Current methods for early screening and detection include the digital rectal exam, or DRE, which entails a physical exam of the prostate, and PSA, which measures levels of another protein known as prostate-specific antigen in the blood.
Both tests are fraught with problems. A high PSA level may signal cancer, but it can also occur in people without prostate cancer. Someone with prostate cancer may not have an elevated PSA. The DRE, based on physician touch and experience, relies on subjective clinical judgment.
Nevertheless, they are the only tests for early detection available and "if a man has a high PSA level and an abnormal DRE, he is referred for a biopsy. But up to 70 percent to 80 percent of men sent for biopsies are found not to have cancer," Keith says.
For early detection of prostate cancer, the American Cancer Society recommends annual PSA and DRE be offered beginning at age 50 to men with at least a 10-year life expectancy. Men with high risk for prostate cancer (African-Americans, family history in first-degree relatives diagnosed before age 65) should start testing at age 45. Men with several first-degree relatives with prostate cancer at an early age could begin testing at age 40. Risks and benefits of testing should be discussed with the patient.
A Better Test for Prostate Cancer
To find a more accurate way to detect prostate cancer, researchers at Panacea developed a test in which they could detect HAAH in the blood.
According to Keith, elevated levels of HAAH have been found in more than 99 percent of tissue samples from more than 20 different cancer types, including liver, breast, ovarian, colon, esophageal, and prostate. In contrast, it was not found in more than 1,000 normal tissue samples. The enzyme is responsible for cell division, movement, and invasion.
The latest research, presented here at a meeting of the American Association for Cancer Research, involved 16 men with prostate cancer and 23 healthy individuals, all of whom had elevated PSA.
Results showed that all the men with prostate cancer had elevated levels of HAAH in the blood, while none of the healthy men did.
"We believe that by adding HAAH to the standard DRE and PSA tests, we can increase the accuracy of early screening for prostate cancer and reduce the number of unnecessary biopsies," Keith says.
D. James Morre, Ph.D., distinguished professor of medicinal chemistry at Purdue University in West Lafayette, Ind., agrees.
The test shows "extreme promise as an adjunct to PSA for the detection of prostate cancer," says Morre, who is researching yet another biomarker for prostate cancer.
Test May Also Show if Treatment Working
Hossein Ghanbari, Ph.D., chief executive officer and chief scientific officer at Panacea, tells WebMD that he is all too familiar with unnecessary biopsies. Due to high PSA levels, he was referred for biopsies three times — and three times was declared cancer-free.
"It's painful; terrible actually," he says. "The last time, they took 24 tissues samples with a very big, fat needle. Then I had to take antibiotics for three or four weeks to avoid infection."
But had the new test been available, Ghanbari says this all may have been avoided. "My blood HAAH level is zero," he says.
Te same test could also be used to monitor response to therapy, Keith says. "If treatment is working, HAAH would basically go back down to zero. If it in fact goes up, that would lead the physician to investigate whether the cancer has returned locally or has spread."
Panacea scientists are planning to kick off a clinical trial within a few weeks in which they will examine HAAH levels in 400 men with prostate cancer and 400 healthy men over age 50.
Additionally, the company is developing a drug to target HAAH. "If you hit it with a monoclonal antibody, you can basically turn it back to normal," Keith says. This in turn, would hopefully help to halt abnormal cell division, movement, and invasion — in other words stop the growth of cancer, he says.
SOURCES: Molecular Diagnostics in Cancer Therapeutic Development Meeting, Chicago, Sept. 12-15, 2006. Stephen Keith, M.D., president and chief operating officer, Panacea Pharmaceuticals, Inc., Gaithersburg, Md. Hossein Ghanbari, Ph.D., chief executive officer and chief scientific officer, Panacea Pharmaceuticals, Inc., Gaithersburg, Md. D. James Morre, Ph.D., distinguished professor of medicinal chemistry, Purdue University, West Lafayette, Ind.
By Charlene Laino
Reviewed by Louise Chang, M.D