Standard cancer treatments not only often fail to eradicate cancer, but can make it worse.
That argument isn't coming from a fringe proponent of alternative medicine, but from the founder of the University of Michigan's Comprehensive Cancer Center and a pioneer in research on why cancers recur and spread to other parts of the body.
The reason breast cancer and other malignancies often return aggressively after treatment is that when tumor cells die under assault from chemotherapy and radiation, they give off substances that can reactivate a special set of master cells known as cancer stem cells, Dr. Wicha said in an interview Tuesday.
Dr. Wicha's lab has found that inflammatory molecules secreted by dying tumor cells can hook up with the stem cells and cause them in effect to come out of hibernation.
He is scheduled to deliver the 2010 Bernard Fisher Lecture at 3:30 p.m. today in Auditorium 6 of Scaife Hall on the University of Pittsburgh campus. The talk, which is free and open to the public, honors Dr. Fisher, a Pitt researcher who pioneered the idea that lumpectomies are just as effective in treating breast cancer as mastectomies.
The existence of cancer stem cells is still controversial in some quarters, Dr. Wicha acknowledged, but is gaining traction.
In the last two months alone, researchers around the nation have published studies on cancer stem cells in breast, ovarian, prostate and brain cancer.
Adult stem cells exist in most tissues, and go into action to repair damage from wounds or infections.
In cancer, they can mutate and no longer obey normal bodily signals to stop growing, Dr. Wicha said.
He and other researchers say that even when chemotherapy and radiation cause tumors to shrink dramatically, these stem cells can stay alive, living under the radar until they are once again spurred into action.
They also believe stem cells are probably the ones that break away from an original tumor and cause cancer to spread elsewhere in the body.
Chemo and radiation kill off the fastest-growing cells in the body, which applies to most cancer cells, but the cancer stem cells that create those rapidly dividing tumor cells actually grow much more slowly themselves, and are less susceptible to those therapies, he said.
One tactic to address this problem is to kill off both types of cancer cells at once, Dr. Wicha said.
A recent experimental trial with advanced breast cancer patients at the University of Michigan, Baylor University in Texas and the Dana-Farber Cancer Institute at Harvard University used standard chemotherapy along with a substance designed to block one of the biochemical pathways of stem cells.
The approach killed off more than 90 percent of the cancer stem cells, Dr. Wicha said, and researchers now hope to expand the treatment to a much larger group of patients.
Ultimately, he hopes cancer treatments can avoid general chemo altogether, with its debilitating side effects, and just use targeted therapies against the stem cells.
There is still a long road ahead, he said, and "my feeling is, to really knock these stem cells out, we're probably going to have to use multiple inhibitors."
Mark Roth: mroth@post-gazette.com or 412-263-1130.
Thursday, February 25, 2010
Friday, February 19, 2010
Doubts About Taking Proscar
Prostate Disorders Special Report
Should You Take Proscar to Prevent Prostate Cancer?
In the quest to find a way to prevent prostate cancer, finasteride (Proscar) was once a rising star -- until evidence showed a potential link between it and high-grade prostate cancer. Now research suggests that this and other concerns are unfounded. But not everyone is convinced. Two Hopkins specialists weigh in on the debate.
The debate began in 2003 with the publication of the Prostate Cancer Prevention Trial (PCPT). In this randomized clinical trial, more than 18,000 men age 55 and older took either 5 mg of Proscar or a placebo every day for seven years. The aim of the study was to determine whether Proscar -- which belongs to the class of medications known as 5-alpha-reductase inhibitors and is commonly prescribed to treat benign prostatic hyperplasia (BPH) -- might also reduce a man's chances of developing prostate cancer.
Results of the PCPT did, in fact, show a 25% reduction in prostate cancer among men taking the drug. But there was a serious catch: Men who developed prostate cancer had an increased likelihood of having higher-grade, more aggressive cancers (Gleason scores of 7 to 10). This finding dampened enthusiasm for using Proscar as a preventive agent against prostate cancer.
New Studies, Different Interpretations -- Two new analyses of the PCPT data -- one published in Urology and the other in Cancer Prevention Research -- were released in May 2008. Each confirms the earlier trial's conclusion that Proscar reduces the risk of prostate cancer. A third analysis published in Cancer Prevention Research re-examined the problem of high-grade tumors. Instead of basing the grade of the prostate cancer on tissue samples from biopsies, the researchers looked at prostate tissue removed from men who underwent radical prostatectomy to treat their prostate cancers. When this tissue was graded, the researchers found that finasteride actually reduced the development of these aggressive prostate cancers by 27% compared with placebo.
Based on these findings, some prostate cancer specialists now support the idea of using Proscar for prostate cancer prevention. But two prominent prostate cancer experts from the Johns Hopkins University School of Medicine -- Patrick C. Walsh, M.D., and H. Ballentine Carter, M.D. -- disagree with these new interpretations.
Two Hopkins Experts Weigh In -- Drs. Walsh and Carter point out that the reduction in prostate cancer cases among men taking Proscar may simply reflect the fact that fewer of these men underwent prostate biopsies. In the PCPT, the men had a for-cause biopsy when there was an abnormality on their digital rectal examination (DRE) or when their PSA level rose higher than 4 ng/mL. Men with a normal DRE and PSA level were offered a biopsy at the end of the seven-year study, but many refused.
The reason: Proscar not only shrinks the prostate but also reduces PSA levels by about half. These artificially low PSA levels in Proscar users can lull some men and their doctors into a false sense of security and prevent needed biopsies.
The finding of a 25% reduction in prostate cancer cases was determined from both the for-cause and end-of-study biopsies. In the real world, however, men only undergo biopsies for cause. When the end-of-study biopsies are removed from the analysis, Proscar users had only a 10% reduction in prostate cancer -- a difference that is much smaller than 25% and is not statistically significant.
The Issue of High-Grade Disease -- So what do the Hopkins experts think about the high-grade tumor problem? First, if the original finding is correct -- that Proscar use increases the risk of high-grade prostate cancer by 68% -- then the drug could do more harm than good in terms of prostate cancer prevention, because at best, it only reduces the overall risk of getting prostate cancer by 25% and at worst, by a mere 10%.
Second, it can't be said with confidence that Proscar reduces the risk of high-grade prostate cancer, because the results of the reanalysis were based on a small number of cases; only 500 men in the study had a prostatectomy.
Our Advice -- Don't take any 5-alpha-reductase inhibitor in hopes of preventing prostate cancer. In addition to Proscar, drugs in this class include Propecia (a form of finasteride used to prevent baldness) and the BPH drug dutasteride (Avodart). If you do use these drugs for BPH or hair loss, there's no need to stop, but it's necessary to get a biopsy right away if your PSA level increases.
Moreover, because 5-alpha-reductase inhibitors lower PSA levels by about 50%, if you use any of these medications you must multiply your PSA by two for the first two years of use, by 2.3 for the second to seventh year, and by 2.5 if you've used the drug for seven or more years. This is extremely important, because if your PSA is rising, your risk of having cancer is three times as high as that of men who don't have a rising PSA, and you're six times as likely to be diagnosed with high-grade disease. Posted in Prostate Disorders on February 18, 2010
Should You Take Proscar to Prevent Prostate Cancer?
In the quest to find a way to prevent prostate cancer, finasteride (Proscar) was once a rising star -- until evidence showed a potential link between it and high-grade prostate cancer. Now research suggests that this and other concerns are unfounded. But not everyone is convinced. Two Hopkins specialists weigh in on the debate.
The debate began in 2003 with the publication of the Prostate Cancer Prevention Trial (PCPT). In this randomized clinical trial, more than 18,000 men age 55 and older took either 5 mg of Proscar or a placebo every day for seven years. The aim of the study was to determine whether Proscar -- which belongs to the class of medications known as 5-alpha-reductase inhibitors and is commonly prescribed to treat benign prostatic hyperplasia (BPH) -- might also reduce a man's chances of developing prostate cancer.
Results of the PCPT did, in fact, show a 25% reduction in prostate cancer among men taking the drug. But there was a serious catch: Men who developed prostate cancer had an increased likelihood of having higher-grade, more aggressive cancers (Gleason scores of 7 to 10). This finding dampened enthusiasm for using Proscar as a preventive agent against prostate cancer.
New Studies, Different Interpretations -- Two new analyses of the PCPT data -- one published in Urology and the other in Cancer Prevention Research -- were released in May 2008. Each confirms the earlier trial's conclusion that Proscar reduces the risk of prostate cancer. A third analysis published in Cancer Prevention Research re-examined the problem of high-grade tumors. Instead of basing the grade of the prostate cancer on tissue samples from biopsies, the researchers looked at prostate tissue removed from men who underwent radical prostatectomy to treat their prostate cancers. When this tissue was graded, the researchers found that finasteride actually reduced the development of these aggressive prostate cancers by 27% compared with placebo.
Based on these findings, some prostate cancer specialists now support the idea of using Proscar for prostate cancer prevention. But two prominent prostate cancer experts from the Johns Hopkins University School of Medicine -- Patrick C. Walsh, M.D., and H. Ballentine Carter, M.D. -- disagree with these new interpretations.
Two Hopkins Experts Weigh In -- Drs. Walsh and Carter point out that the reduction in prostate cancer cases among men taking Proscar may simply reflect the fact that fewer of these men underwent prostate biopsies. In the PCPT, the men had a for-cause biopsy when there was an abnormality on their digital rectal examination (DRE) or when their PSA level rose higher than 4 ng/mL. Men with a normal DRE and PSA level were offered a biopsy at the end of the seven-year study, but many refused.
The reason: Proscar not only shrinks the prostate but also reduces PSA levels by about half. These artificially low PSA levels in Proscar users can lull some men and their doctors into a false sense of security and prevent needed biopsies.
The finding of a 25% reduction in prostate cancer cases was determined from both the for-cause and end-of-study biopsies. In the real world, however, men only undergo biopsies for cause. When the end-of-study biopsies are removed from the analysis, Proscar users had only a 10% reduction in prostate cancer -- a difference that is much smaller than 25% and is not statistically significant.
The Issue of High-Grade Disease -- So what do the Hopkins experts think about the high-grade tumor problem? First, if the original finding is correct -- that Proscar use increases the risk of high-grade prostate cancer by 68% -- then the drug could do more harm than good in terms of prostate cancer prevention, because at best, it only reduces the overall risk of getting prostate cancer by 25% and at worst, by a mere 10%.
Second, it can't be said with confidence that Proscar reduces the risk of high-grade prostate cancer, because the results of the reanalysis were based on a small number of cases; only 500 men in the study had a prostatectomy.
Our Advice -- Don't take any 5-alpha-reductase inhibitor in hopes of preventing prostate cancer. In addition to Proscar, drugs in this class include Propecia (a form of finasteride used to prevent baldness) and the BPH drug dutasteride (Avodart). If you do use these drugs for BPH or hair loss, there's no need to stop, but it's necessary to get a biopsy right away if your PSA level increases.
Moreover, because 5-alpha-reductase inhibitors lower PSA levels by about 50%, if you use any of these medications you must multiply your PSA by two for the first two years of use, by 2.3 for the second to seventh year, and by 2.5 if you've used the drug for seven or more years. This is extremely important, because if your PSA is rising, your risk of having cancer is three times as high as that of men who don't have a rising PSA, and you're six times as likely to be diagnosed with high-grade disease. Posted in Prostate Disorders on February 18, 2010
Wednesday, February 17, 2010
EZH2 Molecule Identifies Aggressive Prostate Cancer
by Ed Edelson | BusinessWeek | 02.15.2010
Harvard researchers report what they say is a major advance toward the long-sought goal of a genetic test that can distinguish between aggressive prostate cancers that require urgent treatment and slow-growing tumors that can safely be left alone.
Today, many men diagnosed with prostate cancer are treated with radiation or chemotherapy even though most of those cancers will grow so slowly that they are not dangerous. It is the cancers that metastasize -- spread outside the prostate gland -- that typically are life-threatening.
"For the first time, we showed in a mouse model that when you take a gene out, you get metastasis and when you put it back in you don't get metastasis," said study author Karen Cichowski, an assistant professor of medicine in the division of genetics at Harvard's Brigham and Women's Hospital. "It looks like the entire pathway is driven by this one gene, the cascade that drives metastasis."
Studies of human prostate cancers have shown the same effect, she said: "We have looked at the genetic pathway in a large number of human tumors, and have found it to be de-regulated in more advanced prostate cancers."
The finding could lead to better treatment of prostate cancer, because the molecule whose production is governed by the gene can be a target of drug therapy, Cichowski said.
The molecule, designated EZH2, is an enzyme, and "enzymes are always good potential therapeutic targets," she said. "Many companies are working to develop EZH2 inhibitors."
The Brigham and Women's program is one of a number being carried out in competitive fashion at several U.S. medical research centers. They are looking at a cluster of genes whose connection with prostate cancer was first described in 2002 by Jer-Tsong Hsieh, a professor of pathology and urology at the University of Texas Southwestern Medical Center at Dallas.
"We complement each other; our findings are very similar," Hsieh said of the Harvard work. "I am a cell biologist and look for the protein. She uses a genetic approach."
Hsieh's group has published several papers on the research, one as recent as last month. One current effort is to develop a chemical reagent that can detect the enzyme, he said.
Another researcher in prostate cancer genetics is Dr. Arul Chinnaiyan, a professor of pathology and urology at the University of Michigan.
The newly reported study "provides a nice mechanistic link as to why EZH2 leads to metastatic cancer," Chinnaiyan said. "It is exciting because there is a lot of interest in the biotechnology world in developing inhibitors of EZH2."
His laboratory is working on such inhibitors, Chinnaiyan added.
"Chinnaiyan showed that this gene for EZH2 is highly expressed in advanced prostate cancer," Cichowski said. "Hsieh showed that a second gene in this genetic pathway was a target of EZH2 and could be silenced by EZH2. It was one of 250 genes targeted by EZH2. We showed that in a mouse model the gene is the primary target of EZH2 in prostate cancer."
That gene, DAB2IP, is suppressed in human prostate cancer, and the degree of suppression correlates with the aggressiveness of a cancer, the journal report said.
"This is the first study to definitively show not only the gene but also the pathway that drives metastasis in prostate cancer," Cichowski said. "Now that we know this pathway, there are many ways to target it."
Copyright BusinessWeek 2010
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About Prostate Cancer | Donate | Get Involved | Programs | Research | Partners | Store | About Us | Site Map | Contact Us | Privacy Policy
Harvard researchers report what they say is a major advance toward the long-sought goal of a genetic test that can distinguish between aggressive prostate cancers that require urgent treatment and slow-growing tumors that can safely be left alone.
Today, many men diagnosed with prostate cancer are treated with radiation or chemotherapy even though most of those cancers will grow so slowly that they are not dangerous. It is the cancers that metastasize -- spread outside the prostate gland -- that typically are life-threatening.
"For the first time, we showed in a mouse model that when you take a gene out, you get metastasis and when you put it back in you don't get metastasis," said study author Karen Cichowski, an assistant professor of medicine in the division of genetics at Harvard's Brigham and Women's Hospital. "It looks like the entire pathway is driven by this one gene, the cascade that drives metastasis."
Studies of human prostate cancers have shown the same effect, she said: "We have looked at the genetic pathway in a large number of human tumors, and have found it to be de-regulated in more advanced prostate cancers."
The finding could lead to better treatment of prostate cancer, because the molecule whose production is governed by the gene can be a target of drug therapy, Cichowski said.
The molecule, designated EZH2, is an enzyme, and "enzymes are always good potential therapeutic targets," she said. "Many companies are working to develop EZH2 inhibitors."
The Brigham and Women's program is one of a number being carried out in competitive fashion at several U.S. medical research centers. They are looking at a cluster of genes whose connection with prostate cancer was first described in 2002 by Jer-Tsong Hsieh, a professor of pathology and urology at the University of Texas Southwestern Medical Center at Dallas.
"We complement each other; our findings are very similar," Hsieh said of the Harvard work. "I am a cell biologist and look for the protein. She uses a genetic approach."
Hsieh's group has published several papers on the research, one as recent as last month. One current effort is to develop a chemical reagent that can detect the enzyme, he said.
Another researcher in prostate cancer genetics is Dr. Arul Chinnaiyan, a professor of pathology and urology at the University of Michigan.
The newly reported study "provides a nice mechanistic link as to why EZH2 leads to metastatic cancer," Chinnaiyan said. "It is exciting because there is a lot of interest in the biotechnology world in developing inhibitors of EZH2."
His laboratory is working on such inhibitors, Chinnaiyan added.
"Chinnaiyan showed that this gene for EZH2 is highly expressed in advanced prostate cancer," Cichowski said. "Hsieh showed that a second gene in this genetic pathway was a target of EZH2 and could be silenced by EZH2. It was one of 250 genes targeted by EZH2. We showed that in a mouse model the gene is the primary target of EZH2 in prostate cancer."
That gene, DAB2IP, is suppressed in human prostate cancer, and the degree of suppression correlates with the aggressiveness of a cancer, the journal report said.
"This is the first study to definitively show not only the gene but also the pathway that drives metastasis in prostate cancer," Cichowski said. "Now that we know this pathway, there are many ways to target it."
Copyright BusinessWeek 2010
This interest
All interests Search:
About Prostate Cancer | Donate | Get Involved | Programs | Research | Partners | Store | About Us | Site Map | Contact Us | Privacy Policy
Saturday, February 6, 2010
ADTs Impact on Individual's Body Composition
Cancer Epidemiology and Prevention Research Group, Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, UK.
The use of androgen deprivation therapy (ADT) in the treatment of prostate cancer is associated with changes in body composition including increased fat and decreased lean mass. Limited information exists regarding the rate and extent of these changes. This systematic review was conducted to determine the effects of ADT on body composition in prostate cancer patients.
Literature searches were conducted on MEDLINE, EMBASE and Web of Science for studies until January 2009. Only longitudinal studies that examined ADT and body composition in prostate cancer patients were included. Data were extracted on body weight, BMI, percentage of fat mass and lean body mass.
Sixteen studies (14 cohorts and 2 RCTs) met the inclusion criteria. Pooled data, calculated according to a random effects model, showed that ADT increased % body fat by on average 7.7% (95% CI 4.3, 11.2, from seven studies, P < 0.0001) and decreased % lean body mass by on average -2.8% (95% CI -3.6, -2.0, from six studies, P < 0.0001) but for both there was marked heterogeneity between studies (I2 = 99% I2 = 73%, respectively). Similarly, body weight (2.1%, P < 0.0001 from nine studies) and BMI (2.2%, P < 0.0001, from eight studies) increased significantly. More extensive changes were seen with longer duration of treatment.
Substantial increases in fat and declines in lean mass were observed in prostate cancer patients treated with ADT. Lifestyle changes or suitable interventions to minimize the effect of ADT on body composition need to be investigated.
Prostate cancer survivors should be made aware of the side effect of treatment on body composition and further work is required to determine what interventions can minimize the impact of ADT on body composition and therefore what evidence based advice they should be provided with. In general, though recommendation of a healthy diet and moderate exercise is reasonable.
Written by:
Haseen F, Murray LJ, Cardwell CR, O'Sullivan JM, Cantwell MM. Are you the author?
Reference:
The use of androgen deprivation therapy (ADT) in the treatment of prostate cancer is associated with changes in body composition including increased fat and decreased lean mass. Limited information exists regarding the rate and extent of these changes. This systematic review was conducted to determine the effects of ADT on body composition in prostate cancer patients.
Literature searches were conducted on MEDLINE, EMBASE and Web of Science for studies until January 2009. Only longitudinal studies that examined ADT and body composition in prostate cancer patients were included. Data were extracted on body weight, BMI, percentage of fat mass and lean body mass.
Sixteen studies (14 cohorts and 2 RCTs) met the inclusion criteria. Pooled data, calculated according to a random effects model, showed that ADT increased % body fat by on average 7.7% (95% CI 4.3, 11.2, from seven studies, P < 0.0001) and decreased % lean body mass by on average -2.8% (95% CI -3.6, -2.0, from six studies, P < 0.0001) but for both there was marked heterogeneity between studies (I2 = 99% I2 = 73%, respectively). Similarly, body weight (2.1%, P < 0.0001 from nine studies) and BMI (2.2%, P < 0.0001, from eight studies) increased significantly. More extensive changes were seen with longer duration of treatment.
Substantial increases in fat and declines in lean mass were observed in prostate cancer patients treated with ADT. Lifestyle changes or suitable interventions to minimize the effect of ADT on body composition need to be investigated.
Prostate cancer survivors should be made aware of the side effect of treatment on body composition and further work is required to determine what interventions can minimize the impact of ADT on body composition and therefore what evidence based advice they should be provided with. In general, though recommendation of a healthy diet and moderate exercise is reasonable.
Written by:
Haseen F, Murray LJ, Cardwell CR, O'Sullivan JM, Cantwell MM. Are you the author?
Reference:
aspirin and other NSAIDs Impact on Prostate Cancer
Thursday, 04 February 2010
Department of Oncology, McGill University, Montreal, Canada.
The association between use of aspirin and other NSAIDs and the risk of prostate cancer remains controversial despite many observational epidemiological studies. We conducted a systematic meta-analysis of these studies to examine both the strength and the consistency of the association, and to explore sources of variability between studies. We searched 12 computerized literature databases for reports published before June 2008, and included any epidemiologic studies where the outcome was prostate cancer incidence or mortality, and the exposure was use of NSAIDs.Studies that met the inclusion criteria comprised 10 case-control and 14 cohort studies with a total of 24,230 prostate cancer cases. Studies that assessed the effect of aspirin use on total prostate cancer had a pooled OR (POR) of 0.83 (95%CI: 0.77-0.89) whereas those that assessed the effect of aspirin on advanced prostate cancer had a POR of 0.81 (0.72-0.92). Studies that examined the effects of non-aspirin NSAIDs or all NSAIDs were less consistent but still suggestive of reduced risks. However, most reviewed studies were limited by exposure and disease misclassification, by inadequate information on dose and duration of use and by the possibility of screening and other biases.In conclusion, the epidemiologic evidence for a protective effect of aspirin and other NSAID use against prostate cancer is suggestive but not conclusive. There is a need for well-designed observational studies with adequate exposure measurements, accurate case definition, attention to latency effects, and careful adjustment for screening and other biases.
Written by:
Mahmud SM, Franco EL, Aprikian
Department of Oncology, McGill University, Montreal, Canada.
The association between use of aspirin and other NSAIDs and the risk of prostate cancer remains controversial despite many observational epidemiological studies. We conducted a systematic meta-analysis of these studies to examine both the strength and the consistency of the association, and to explore sources of variability between studies. We searched 12 computerized literature databases for reports published before June 2008, and included any epidemiologic studies where the outcome was prostate cancer incidence or mortality, and the exposure was use of NSAIDs.Studies that met the inclusion criteria comprised 10 case-control and 14 cohort studies with a total of 24,230 prostate cancer cases. Studies that assessed the effect of aspirin use on total prostate cancer had a pooled OR (POR) of 0.83 (95%CI: 0.77-0.89) whereas those that assessed the effect of aspirin on advanced prostate cancer had a POR of 0.81 (0.72-0.92). Studies that examined the effects of non-aspirin NSAIDs or all NSAIDs were less consistent but still suggestive of reduced risks. However, most reviewed studies were limited by exposure and disease misclassification, by inadequate information on dose and duration of use and by the possibility of screening and other biases.In conclusion, the epidemiologic evidence for a protective effect of aspirin and other NSAID use against prostate cancer is suggestive but not conclusive. There is a need for well-designed observational studies with adequate exposure measurements, accurate case definition, attention to latency effects, and careful adjustment for screening and other biases.
Written by:
Mahmud SM, Franco EL, Aprikian
Tuesday, February 2, 2010
Interesting New MetastaticProstate Cancer Study
New Metastatic Prostate Cancer Research Study
Have you been diagnosed with metastatic prostate cancer? You may be eligible to participate in a research study that would involve completing one telephone interview lasting approximately 1 hour. During the interview, you will be asked about your experiences with metastatic prostate cancer. You will be compensated for your time.
If you are interested, please contact Shadi at shadi.gholizadeh@oxfordoutcomes.com or call 240-482-0034 x 25.
The name of the research study is NewMetastaticCancerReferenceStudy.doc
Looks interesting!
Have you been diagnosed with metastatic prostate cancer? You may be eligible to participate in a research study that would involve completing one telephone interview lasting approximately 1 hour. During the interview, you will be asked about your experiences with metastatic prostate cancer. You will be compensated for your time.
If you are interested, please contact Shadi at shadi.gholizadeh@oxfordoutcomes.com or call 240-482-0034 x 25.
The name of the research study is NewMetastaticCancerReferenceStudy.doc
Looks interesting!