Howard Waage ---- Editor
Where: Our meeting will be in the Bennett & Suzy Katz Cancer Resource Center on the 1st Floor of the two-story redwood Education Building behind Santa Cruz Dominican Hospital.
When: Tuesday, July 27th, 2010 at 7:00 p.m.. For more information, please cal The Bennett and Suzy Katz Cancer Resource Center at Dominican Hospital (831) 462-7770
By Melinda Beck. The Wall Street Journal – (June 29, 2010) Scientists may soon be able to answer the agonizing question facing men with prostate cancer: Does their cancer need immediate treatment or can it be left alone?
Some 218,000 American men will be diagnosed with prostate cancer this year. An estimated 85% of those tumors will grow so slowly that they will never cause problems. But the rest are aggressive and lethal. As of now, there's no way to tell early on which cancers are which, so tens of thousands of men undergo surgery or radiation each year for cancers that never needed treatment, risking impotence or incontinence in the process.
Several recent genetic discoveries could help doctors evaluate how aggressive a man's prostate cancer is much earlier. Scientists at the University of Michigan have identified at least 24 different kinds of prostate cancer of varying virulence whose DNA signatures can be read like a bar code. Memorial Sloan-Kettering Cancer Center researchers have identified other genetic subtypes of prostate cancer that seem to predict whether the tumor will be low or high risk. And Harvard Medical School scientists have found a specific gene that causes prostate cancers to spread. Some of the discoveries also could lead to new treatments, tailored specifically for the kind of prostate tumor a man has.
Such genetic tests for prostate cancers would go well beyond the current PSA test (for prostate-specific antigen) used for screening men in general. PSA tests have helped find prostate cancers at much earlier stages, saving thousands of lives in recent years. But PSA levels also rise for reasons that have nothing to do with cancer, prompting many men to have prostate biopsies each year that don't find cancer or that find tumors of the slow-growing variety.
Scientists say new prostate-cancer tests could be available in the not-too-distant future. "It won't be tomorrow, but if you go by the pace at which such technology entered the field of breast cancer, it will be several years [for new prostate tests], not a decade," says Charles Sawyers, chairman of human oncology and pathogenesis at Memorial Sloan-Kettering.
At the University of Michigan, researchers have focused mainly on what are known as gene fusions, in which DNA from some genes gets stuck to other genes, altering what they do. Two of the 24 types they have identified involve the same gene, known as RAF, that drives malignant melanoma, according to a report in the journal Nature Medicine this month. Although those two types make up only about 2% of the tumors studied so far, they are highly aggressive, killing an estimated 3,600 men each year.
Treatment for those prostate cancers is on the horizon. Several anti-RAF drugs to treat melanoma have regulatory approval or are in late-stage clinical trials. Early lab tests show that some of those drugs are effective against RAF prostate-cancer cells.
Researchers are closing in on ways to determine whether a prostate tumor is likely to metastasize, based on gene analyses. Most of the remaining prostate-cancer types involve fusions of a gene called ETS, and they are more or less virulent depending on which fragments of other genes are fused to them. Jonathan Simons, chief executive officer of the Prostate Cancer Foundation, which funds much of the Michigan research, likens the process to rebuilding car engines out of random automotive parts. "If you have a tumor with a lawn-mower engine, it may look like a cancer, we may call it a cancer, but it may never be a problem in the life of a 72-year old man," he says. "But if you have a cancer with a bulky Dodge Hemi stuck to a BMW 850csi V-12 engine, that needs treatment."
Four of the 24 cancer types discovered, which together make up over 50% of the prostate cancers classified so far, have the equivalent of lawn-mower engines and probably don't have enough power to grow past the prostate gland, Dr. Simons says. Another 20% are more highly powered and could pose problems in the presence of other gene fusions.
And one of the most aggressive types, representing 10% to 15% of prostate cancers, appears to follow a different mechanism: It results when there are excess amounts of a protein known as SPINK1. Since the protein shows up in urine, the researchers say a urine test could be designed to measure its presence.
There could be more types, represented by different genetic bar codes. "We are finding more every month or so, filling in the gaps," says the lead investigator Arul Chinnaiyan, director of the Michigan Center for Translational Pathology. To validate the findings, researchers, who so far have studied some 300 tumor samples, plan to analyze at least 1,000 samples and to follow how the patients progress. "We are not there yet, but within the next year, we hope to have a clinical lab test where we can predict what kind of cancer a man has," says Dr. Chinnaiyan.
Researchers at Memorial Sloan-Kettering are studying a different kind of genetic error involved in prostate cancer. Instead of two copies of a gene, some cancer cells have too many or too few, known as copy-number alterations.
In a study in the journal Cancer Cell last week, the researchers analyzed the copy-number alterations in 218 cancerous prostates surgically removed at Sloan-Kettering and found that they fell into six clusters. Those clusters corresponded closely with how quickly the patients' cancer returned, judging by their PSA. "It was a surprise to us that so much prognostic information was there in the original samples after surgery," Dr. Sawyers says. Ideally, "we'd be able to tell a man, 'Your tumor looks like it's in cluster five, so you should get surgery and radiation and perhaps even more aggressive therapy. Or, you are in cluster two, so you can relax and maybe just get another biopsy in another year and see if your cluster has changed," he says.
Further testing at Sloan Kettering is continuing. The researchers have 1,000 additional samples from prostates removed more than 10 years ago and can correlate their findings with how the patients fared in that time.
In still another recent breakthrough, researchers at Harvard Medical School identified a gene pathway directly involved in prostate-cancer metastasis. They isolated a gene, DAB2IP, that acts as a brake for cancer. When too much of an enzyme, EZH2, is present, the DAB2IP gene is suppressed, removing the brake and allowing the cancer to spread.
"It's more than just correlation; it's cause and effect," says lead researcher Karen Cichowski, a cancer biologist, who demonstrated the process in mice in a study in Nature Medicine this year. The Harvard researchers also studied data from human prostate cancers and found that the patients with the most aggressive tumors had either excess EZH2 or too little DAB2IP or both. These findings, too, could yield tests to predict how aggressive a patient's prostate cancer could be. Several biotech companies have drugs in the works to inhibit EZH2.
The various research findings complement each other by describing different ways that genes mutate as cancers evolve, says Dr. Chinnaiyan. He expects that diagnostic tests in the future will look at a variety of genes, as well as proteins, molecules and other "biomarkers" to predict how aggressive a cancer might be.
Another technique being applied to prostate cancer involves magnetic resonance spectroscopy, a form of imaging that tracks chemical changes in tissues. In a small study in the journal Science Translational Medicine this year, researchers at Harvard showed that the scanning technology can not only locate cancers within the prostate, but also has the potential to distinguish fast and slow-moving cancers.
Progress is also being made on ways to measure prostate cancers through simple blood and urine tests, or what scientists call "liquid biopsies." The biotech firm Gen-Probe Inc., working with the University of Michigan researchers, has developed a test for a gene called PCA3 that shows up in urine only when a man has prostate cancer.
For now, the PCA3 test is mainly useful to tell men who have a rising PSA level that they should have a biopsy as well, or for men who have a negative biopsy that might have missed cancer. Dr. Chinnaiyan hopes the PCA3 test can also check for gene fusions that can identify which type of prostate cancer a man has. The PCA3 test is not yet approved by the Food and Drug Administration, but it is approved for use in Europe and is available in several U.S. labs on an investigational basis.
In other prostate-cancer news, there's more evidence that cholesterol-lowering statin drugs may play a role in controlling the spread of prostate cancer. In a study in the journal Cancer, researchers at Duke University Medical Center and elsewhere analyzed the records of 1,319 men who had their prostates removed between 1988 and 2008 and found that 304 of them had a rising PSA level after surgery, which generally indicates that the cancer has reoccurred and spread. Men who were taking the equivalent of 20 mg of simvastatin a day were 43% less likely to see a recurrence. In men taking a higher dose, the risk of recurrence was reduced by 50%.
The researchers cautioned that the reduced risk could be due to factors other than statins, such as diet, exercise or smoking habits; only a randomized clinical trial could tell for sure. Five other recent studies also have found that statins appear to lower the risk for advanced prostate cancer. Source: http://online.wsj.com/article/SB10001424052748703279704575334982806405218.html
A new report in the Federation of American Societies for Experimental Biology Journal suggests that disrupting a particular cellular signaling pathway could stop or slow the initiation, promotion, and progression of prostate cancer.
In what could lead to a major advance in the treatment of prostate cancer, scientists now know exactly why polyphenols in red wine and green tea inhibit cancer growth. This new discovery, published online in The FASEB Journal (http://www.fasebj.org), explains how antioxidants in red wine and green tea produce a combined effect to disrupt an important cell signaling pathway necessary for prostate cancer growth. This finding is important because it may lead to the development of drugs that could stop or slow cancer progression, or improve current treatments.
"Not only does SphK1/S1P signaling pathway play a role in prostate cancer, but it also plays a role in other cancers, such as colon cancer, breast cancer, and gastric cancers," said Gerald Weissmann, MD, editor-in-chief of The FASEB Journal. "Even if future studies show that drinking red wine and green tea isn't as effective in humans as we hope, knowing that the compounds in those drinks disrupts this pathway is an important step toward developing drugs that hit the same target."
Scientists conducted in vitro experiments which showed that the inhibition of the sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway was essential for green tea and wine polyphenols to kill prostate cancer cells. Next, mice genetically altered to develop a human prostate cancer tumor were either treated or not treated with green tea and wine polyphenols. The treated mice showed reduced tumor growth as a result of the inhibited SphK1/S1P pathway. To mimic the preventive effects of polyphenols, another experiment used three groups of mice given drinking water, drinking water with a green tea compound known as EGCg, or drinking water with a different green tea compound, polyphenon E. Human prostate cancer cells were implanted in the mice and results showed a dramatic decrease in tumor size in the mice drinking the EGCg or polyphenon E mixtures.
"The profound impact that the antioxidants in red wine and green tea have on our bodies is more than anyone would have dreamt just 25 years ago," Weissmann added. "As long as they are taken in moderation, all signs show that red wine and green tea may be ranked among the most potent 'health foods' we know." Source: http://www.eurekalert.org/pub_releases/2010-06/foas-pir060910.php (June 9th, 2010)
ScienceDaily (June 28, 2010) - Men who use statins to lower their cholesterol are 30 percent less likely to see their prostate cancer come back after surgery compared to men who do not use the drugs, according to researchers at Duke University Medical Center. Researchers also found that higher doses of the drugs were associated with lower risk of recurrence.
The findings are published in the journal Cancer. "The findings add another layer of evidence suggesting that statins may have an important role in slowing the growth and progression of prostate cancer," says Stephen Freedland, M.D., a member of the Duke Prostate Center and the Urology Section at the Durham Veterans Affairs Medical Center, and the senior author of the study. "Previous studies have shown that statins have anti-cancer properties, but it's not entirely clear when it's best to use them -- or even how they work."
Researchers examined the records of 1319 men who underwent radical prostatectomy included in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. They found that 18 percent of the men -- 236 -- were taking statins at the time of surgery.
Researchers followed the patients after surgery to evaluate recurrence rates, measured by slight rises in the PSA levels after surgery, a development known as "biochemcical recurrence." Time to biochemical recurrence is viewed as an important clinical factor because it is correlated with the risk of disease progression and death.
The authors found that 304 men had a rising PSA, including 37 (16 percent) of the statin users and 267 (25 percent) of the non-users. Taking into account various clinical and pathological features that differed between the two groups, the data showed that overall, statin use reduced the risk of biochemical recurrence by 30 percent.
Among men taking statins equivalent to 20 mg of simvastatin a day, the risk of recurrence was reduced 43 percent and among the men taking the equivalent of more than 20 mg of simvastatin a day, the risk of recurrence was reduced 50 percent. Men who took a statin dose the equivalent of less than 20 mg of simvastatin daily saw no benefit.
There were significant differences between those who took the drugs and those who did not. Statin users tended to be white, older and heavier than non-users. They also had lower clinical stages at diagnosis, but higher Gleason scores, a measure of tumor aggressiveness.
"These findings are intriguing, but we do need to approach them with some caution," says Robert Hamilton, M.D., a urologist at the University of Toronto and the lead author of the study. "For example, we don't know the diet, exercise or smoking habits of these men. So it's not entirely clear if the lower risk we detected is related to the statins alone -- it could be due to other factors we were not able to measure. We do feel, however, that based on these findings and those from other studies, the time is ripe to perform a well-controlled randomized trial to test whether statins do indeed slow prostate cancer progression."
The study was funded by the Department of Defense, Prostate Cancer Research Program; the Department of Veterans Affairs, the National Institute of Health, the Georgia Cancer Coalition and the American Urological Association Foundation. Source: http://www.sciencedaily.com/releases/2010/06/100628075413.htm
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Below are online resources for learning about your prostate cancer. "Prostate Cancer Websites" includes some of the more popular locations for newly diagnosed patients to do research, with links to more specialized sites where patients may go to get answers and do their “homework”. NOTE: The resources listed here are not a substitute for professional medical advice. Always consult qualified medical resources before making any treatment decision.
The Santa Cruz County Prostate Cancer Support Group maintains quite a few up to date books and videos about prostate cancer, prevention, diagnosis and treatment options for anyone interested in doing research or needs information about this disease. The library is located at the Katz Cancer Resource Center Dominican Hospital Education Building 1555 Soquel Drive, Santa Cruz, CA Open 9 a.m. to 4 p.m. Monday through Thursday 10 a.m. to 2 p.m. Friday or by Appointment (831) 462 7770.
Our support group has ongoing operating expenses beyond what our sponsors can provide. We do not have dues, but hope members will consider making any size donation to help us. Donations are welcome to assist us in maintaining and expanding our programs within the local community including the costs to run our website. The funds also help in keeping our library up to date with up to date books and literature regarding the treatment of prostate cancer, managing side affects, active surveillance, as well as information on nutrition, diet and lifestyle. Please make checks payable to "Santa Cruz County Prostate Cancer Support Group" and mail to:
Santa Cruz County Prostate Cancer Support Group
C/O Howard Waage
63 Asta Drive
La Selva Beach, CA 95076
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Many THANKS to the American Cancer Society for assisting with the printing and mailing of this newsletter and the Katz Cancer Resource Center for allowing us to use their facility.