Bielas, Mostaghel secure three-year funding for prostate-cancer research

December 7, 2009 by · Leave a Comment 

Drs. Elahe Mostaghel and Jason Bielas recently received New Investigator Awards from the Department of Defense’s Prostate Cancer Research Program.

Bielas, an investigator in the Public Health Sciences Division, will use his three-year, $365,000 grant to develop a blood-based, non-invasive screening test to diagnose prostate cancer and determine its stage by monitoring the prevalence of tumor-associated mitochondrial DNA mutations at very precise levels. Currently, suspected prostate cancer is typically confirmed by taking a biopsy of the prostate and further tests like CT and bone scans are used to determine whether prostate cancer has spread. Bielas hopes the new markers will be predictive of the biological behavior of prostate tumors, which would guide the type and aggressiveness of therapy used. He believes his findings could be applied to other cancers.

The Human Biology Division’s Mostaghel received total funding of $225,000 for three years. She will evaluate how prostate tumor cells respond to treatment that targets the production of testosterone not only in the blood, but in the tumor itself, by using new drugs under development that can block the testosterone synthesis machinery inside the tumor cells. Mostaghel will compare tumor response to currently available prostate cancer drugs versus a new powerful drug, VN-124.

“While we predict tumor cells will respond better to VN-124, the real goal is to understand the biology of the prostate cancer cell as it develops resistance to therapy,” Mostaghel said. “Ideally, hormonal therapy would completely eliminate or cure the prostate cancer cell. However, it is more likely that over time, the tumor cells will develop resistance mechanisms which may be different from currently understood pathways of resistance.” This understanding, she said, will help identify the relevant molecular pathways to target in the future.

Since its inception in 1997, the Prostate Cancer Research Program has received $890 million in congressional appropriations and remains the world’s second-largest funding agent of extramural prostate cancer research. The program uses innovative approaches, including input from consumer advocates, to funnel these funds directly into innovative research to accelerate discovery, translate discoveries into clinical practice, and improve the quality of care for men with prostate cancer.

This article has been reprinted from http://www.fhcrc.org/about/pubs/center_news/online/2009/12/DOD_grants.html. Written By COLLEEN STEELQUIST.

Dr. Nelson to lead Canary Foundation’s Prostate Consortium

May 5, 2008 by · Leave a Comment 

Researchers at the Hutchinson Center have a lead role in a new public/private partnership to create the first systematic surveillance program of men with prostate cancer to look for biological clues to help determine when to wait and when to treat the disease. The Canary Foundation and the National Cancer Institute announced the project on Friday.

Dr. Pete Nelson, of the Clinical Research and Human Biology divisions, will lead the Canary Prostate Consortium. This group of six institutions nationwide will enroll men in a cancer-surveillance study to look for biomarkers—proteins in the blood that could predict prostate-tumor aggressiveness.

The Prostate Active Surveillance Study is meant to help answer a key question that has vexed physicians and researchers: When is it best to treat prostate cancer versus observation or “watchful waiting.” For most men with prostate cancer, the disease never progresses to become a serious health problem, yet most receive some sort of treatment, such as radiation or surgery. Such treatments can have side effects, such as impotence and incontinence, which can be worse than the low-grade cancer. Currently it is challenging to accurately predict when inactive or slow-growing prostate tumors will become aggressive.

“There’s an emerging consensus that we dramatically over treat prostate cancer in general,” Nelson said. “The overall prevalence of the disease in the population far exceeds the number of men whose disease progresses to cause serious problems. Yet, there are clearly many prostate cancers that behave aggressively and patients benefit from treatment. It is a challenging problem.”

In the study, men diagnosed with early stage prostate cancer will not be treated right away but will be closely followed in an active surveillance program involving regular collection of blood and urine samples as well as prostate biopsies. A new repository for blood and DNA samples will be housed at the Center and funded by the Canary Foundation. NCI’s Early Detection Research Network (EDRN), the federal agency that is partnering with the Canary Foundation, will establish disease-specific Common Data Elements, a biospecimen management system and a protocol oversight program. The EDRN data management and coordinating center is based at the Hutchinson Center under the direction of Dr. Zideng Feng of the Public Health Sciences Division.

The samples will be tested for proteins in the blood that can signal when indolent disease has progressed to more aggressive illness. Such biomarkers could help physicians better determine when to initiate treatment versus watchful waiting.

The Canary Foundation is providing initial funding for the Prostate Active Surveillance Study. The five institutions that will enroll patients are University of Washington, Stanford University, University of California at San Francisco, University of British Columbia and University of Texas Health Science Center in San Antonio.

This article has been reprinted from http://www.fhcrc.org/about/pubs/center_news/online/2008/pete_nelson.html. Written by DEAN FORBES.

Hutchinson Center researchers gaining ground in fight against prostate cancer

December 1, 2007 by · Leave a Comment 

Prostate Gland Adenocarcinoma

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.

Prostate gland may be capable of buffering negative effects of TRT

January 20, 2007 by · Leave a Comment 

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.

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