From promising new medications and imaging techniques to improved understanding of molecular features and disease predictors, Hutchinson Center scientists are gaining ground in battling prostate cancer, the second leading cause of cancer deaths in men. An estimated 218,800 American men will be diagnosed with prostate cancer this year
“Our comprehensive, multidisciplinary group of researchers and doctors are increasing what is known about the genetic, environmental and lifestyle causes of prostate cancer,” said Dr. Janet Stanford, head of the Hutchinson Center’s Program in Prostate Cancer Research. “We’re discovering how these factors play a role in more aggressive prostate cancer, cancer recurrence and progression of the disease after therapy, and how this information can be used to develop new prostate-cancer prevention strategies. We’re also working toward more effective treatments to improve patient outcomes.”
Improving the power of prediction
Prostate cancer — unlike many cancers — is a disease with which many men can live. Prostate tumors tend to grow very slowly and are often better left untreated. But some tumors behave badly, ignoring the normal cell growth-control mechanisms. Such cancer can aggressively spread and is often lethal. So the question becomes how to foresee which is which.
Dr. Pete Nelson and colleagues pinpointed molecular features to help predict how prostate-cancer cells will behave. Their findings could help identify genes to target for therapy and point to possible markers of aggressive prostate cancer in the blood.
The current method for predicting outcome looks at the cancer under a microscope and grades, or visually describes, the cells. Prostate cancer has a specific grading system called a Gleason grade, and while it’s often accurate, it’s very subjective. Over-treatment of nonaggressive prostate cancer brings significant side effects, which impact a man’s quality of life.”The issue with prostate cancer hasn’t been diagnosing it, but diagnosing the ones that really need treatment,” Nelson said.
In a new approach, Nelson’s team looked at 86 different genes, and they were able to determine what genes were turned on in low- or high-grade prostate-cancer cells with great accuracy. The study represents the first systematic attempt to distinguish these molecular features to produce a more objective predictor of how an individual’s prostate cancer will behave.
The scientists also found a significant association between more aggressive cancers and high levels of a protein called monoamine oxidaseA (MAOA). MAOA-inhibiting drugs have been used to treat depression for many years. “These drugs are readily available, so we’re doing some experiments now to see if inhibiting MAOA will affect the growth of cancer cells,” Nelson said.
Seeing tumors without surgery
Cancer researchers are eager to develop visual cancer-detection tests for two key reasons: They are noninvasive and can provide doctors with detailed disease information much faster than many conventional methods.
Even when tumors are smaller than the head of a pin and long before they cause symptoms, scientists may be able to spot them using imaging coupled with injected tracer molecules that target cancer cells and light them up.
Such imaging can be used to spot the earliest signs that a cancer has spread from the site of the original tumor to distant parts of the body. Nelson is using this approach with mice in order to understand how aggressive prostate tumors spread to bones and other tissues.
“We also would like to use imaging to clearly see different parts of a tumor, which may have very different properties,” Nelson said. “This will help us to learn which types of cells contribute to the development of aggressive disease, which will ultimately help us to detect it earlier and treat it more effectively.”
Lessening side effects
Muscle wasting is a significant problem for prostate-cancer patients who have been treated with hormonal therapy. Dr. Celestia (Tia) Higano, a prostate-cancer specialist at the Seattle Cancer Care Alliance, is conducting a trial of a new drug that may help restore muscle. “We’re giving this new drug to men who have been on androgen deprivation for their prostate cancer to see if it builds muscle after one month,” Higano said.
If the results are promising, Higano believes the drug study may be expanded for use in patients with AIDS and other diseases that cause muscle wasting. Some research has shown evidence that preventing muscular atrophy may decrease mortality.
Decoding prostate cancer’s biology
Dr. Alan Kristal co-leads an international research team to study the mechanisms of prostate-cancer prevention. The scientists are analyzing blood, DNA, prostate biopsy tissue and surgery tissue taken from nearly 19,000 study participants in an attempt to generate insights into the molecular biology of prostate cancer.
The Prostate Cancer Prevention Trial tested whether the drug finasteride would reduce the rate of prostate cancer. While the study found that the drug cut the chance of developing prostate cancer by nearly 25 percent, it also increased the risk of developing more lethal prostate cancer in some men.
The current study looks at behavioral, metabolic and genetic influences on prostate-cancer risk, which may shed light on when and how to best use finasteride for cancer prevention.
This article was reprinted from Quest Online, a publication of the Fred Hutchinson Cancer Research Center, at http://www.fhcrc.org/about/pubs/quest/articles/2007/12/cancer_killer.html. Written byBy Colleen Steelquist.
In 1966, investigators at the University of Chicago won a Nobel Prize for their research on the relationship between male sex hormones, known as androgens, and prostate cancer. Forty years later, researchers are still working out the intricacies of that relationship.
A recent study co-authored by the Center’s Dr. Peter Nelson (pictured left) reports that testosterone-replacement therapy (TRT) for men with low testosterone levels has minimal effect on the prostate gland over a period of six months. Previous studies indicated that this therapy might be harmful.
“It’s pretty well known that androgens are very important for the initiation as well as the progression of prostate cancer. Without any testosterone, prostate cancer essentially never develops,” said Nelson, an investigator in the Human Biology Division. “Eliminating testosterone is the most active form of treatment in very advanced disease. There’s been a lot of interest in studying testosterone in the context of prostate cancer.”
The new study, which was led by Dr. Leonard Marks of the Urological Sciences Research Foundation and the University of California, Los Angeles, was published in the Nov. 15 issue of the Journal of the American Medical Association. Researchers studied 44 men with low serum testosterone levels between the ages of 44 and 78 years. What they anticipated and found was that TRT increased serum testosterone levels to the mid-normal range. More unexpectedly, TRT only slightly increased androgen levels in prostate tissue, and urinary symptoms, which can be affected by growth of prostate tissue, were found to be similar between the placebo and testosterone- treated groups.