Adding hormone therapy to radiation therapy has been proven in randomized clinical trials to improve overall survival for men with intermediate- and high-risk prostate cancer. However, adding hormone therapy may reduce overall survival in men with pre-existing heart conditions, even if they have high-risk prostate cancer according to a new study just published online in advance of print in the International Journal of Radiation Oncology•Biology•Physics, the official scientific journal of ASTRO.
From 1991 to 2006, 14,594 men with prostate cancer were treated with brachytherapy-based radiation therapy. Of these, 1,378 (9.4 percent) had a history of congestive heart failure or myocardial infarction. Among these men with heart conditions, 22.6 percent received supplemental external beam radiation therapy and 42.9 percent received four months of androgen deprivation therapy to reduce testosterone in their bodies, which can help the cancer grow.
For the entire group of men with a history of heart problems, adding hormone therapy led to a significant increase in overall mortality. For men with pre-existing heart conditions and high-risk prostate cancer, researchers found that by 5 years, 31.8 percent of the men who received hormones had died compared to 19.5 percent of the men who did not receive hormone therapy.
"We found that for men with localized prostate cancer and a history of heart problems, treatment with hormones plus radiation was associated with a higher all-cause mortality than treatment with radiation alone, even for patients with high-risk malignant disease," Paul L. Nguyen, M.D., lead author of the study and a radiation oncologist at the Dana-Farber/Brigham and Women's Cancer Center in Boston, said. "Despite Phase III data supporting hormone therapy use for men with high-risk disease, the subgroup of men with a history of heart disease may be harmed by hormone therapy."
He added, "Future research is necessary to understand the mechanisms of this effect. In the meantime, I encourage men with prostate cancer and a history of heart disease to talk to their doctor about the benefits and risks of hormone therapy."
Tuesday, July 26, 2011
Monday, July 11, 2011
Nearly all patients with high-grade bladder cancer do not receive guideline-recommended care
A study at UCLA's Jonsson Comprehensive Cancer Center found that nearly all patients with high-grade, non-invasive bladder cancer are not receiving the guideline-recommended care that would best protect them from recurrence, a finding that researchers characterized as alarming.
In fact, out of the 4,545 bladder cancer patients included in the study, only one received the comprehensive care recommended by the American Urology Association and the National Comprehensive Cancer Network.
Receiving the recommended comprehensive care for high-grade bladder cancer is critical because it can significantly minimize the likelihood that patients will die from their cancer, said Dr. Karim Chamie, a postdoctoral fellow in urologic oncology and health services research and lead author of the study.
"We were surprised by the findings in this study, particularly in an era when many suggest that doctors over-treat patients and do too much in the name of practicing defensive medicine," Chamie said. "This study suggests quite the contrary, that we don't do enough for patients with bladder cancer. If this was a report card on bladder cancer care in America, I'd say we're earning a failing grade."
The study is published July 11, 2011 in the early online edition of CANCER, a peer-reviewed journal of the American Cancer Society.
The study then investigated the cause of poor compliance. What they found was that non-compliance knew no boundaries and that patient-level factors such as age, race, ethnicity or socioeconomic status had very little impact. Instead, non-compliance with guideline-recommended care was primarily attributed to urologists. The patients in the study were elderly, but capable of withstanding these simple measures.
"It wasn't their age, race, ZIP code or how wealthy they were. It all came down to who their doctor was," Chamie said
Dr. Mark S. Litwin, professor of urology and public health and senior author of the study, said it's not clear why physicians are not routinely following established guidelines for care.
"It is puzzling, because strong evidence supports those guidelines," Litwin said. "But this is a wake-up call to all physicians caring for patients with bladder cancer. We know definitively what constitutes high-quality care. Now we just need to make sure it happens."
Patients with primary high-grade bladder cancer, which has not yet invaded the muscle of the bladder, have a 50 to 70 percent chance of their cancer coming back in the bladder following treatment. They also have a 30 to 50 percent chance of the cancer becoming more aggressive and invading into the muscle, where it is much harder to treat. Once the cancer invades the muscle, the bladder and surrounding organs must be removed and both the quality and the quantity of the patient's life are significantly impacted, Chamie said.
Chamie said that, at diagnosis, about 75 percent of bladder patients have disease that has not invaded the muscle. So treating those patients with the guideline-recommended care to help minimize recurrences and prevent invasion of the tumor into the muscle could help a large number of patients.
The recommended medical guidelines call for injecting a cancer-killing drug directly into the bladder to minimize recurrence and progression. They also recommend an intense follow-up schedule, including the repeated use of a scope to evaluate the bladder from the inside, a procedure called cystoscopy, and a urine test that is similar to a pap smear every three months to check for abnormal cells.
Only one patient in the study, which analyzed date from Surveillance, Epidemiology and End Results (SEER)-Medicare linked database, was given the recommended care. The study also found that nearly half of urologists treating these patients had not performed at least one cystoscopy, one urine test, and one infusion of the cancer-killing drug into the bladder.
To rectify the situation, Chamie and Litwin suggest a quality-improvement initiative and or changes to physician reimbursements. To complicate matters, despite the poor compliance rate, bladder cancer is the most expensive malignancy to treat on a per-patient level. While improving compliance with changes to physician reimbursement or a quality improvement initiative will increase healthcare costs in the short term, preventing recurrences or progression of the cancer likely will cut costs in the long term.
"We have to improve compliance and there are two ways to do that: Modify our reimbursement schedules to provide incentives to doctors to follow the guidelines, or go out and interact and educate the community urologists - who are delivering the vast majority of bladder cancer care - on the importance of providing compliant care," Chamie said. "Unlike some patients diagnosed with bladder cancer after having it spread to other sites when it's too late to treat effectively, or those with low-grade tumors that are not likely to ever be aggressive, this is a potentially curable cohort of patients. If we don't do a good enough job treating these cancers, we're going to lose these patients."
In fact, out of the 4,545 bladder cancer patients included in the study, only one received the comprehensive care recommended by the American Urology Association and the National Comprehensive Cancer Network.
Receiving the recommended comprehensive care for high-grade bladder cancer is critical because it can significantly minimize the likelihood that patients will die from their cancer, said Dr. Karim Chamie, a postdoctoral fellow in urologic oncology and health services research and lead author of the study.
"We were surprised by the findings in this study, particularly in an era when many suggest that doctors over-treat patients and do too much in the name of practicing defensive medicine," Chamie said. "This study suggests quite the contrary, that we don't do enough for patients with bladder cancer. If this was a report card on bladder cancer care in America, I'd say we're earning a failing grade."
The study is published July 11, 2011 in the early online edition of CANCER, a peer-reviewed journal of the American Cancer Society.
The study then investigated the cause of poor compliance. What they found was that non-compliance knew no boundaries and that patient-level factors such as age, race, ethnicity or socioeconomic status had very little impact. Instead, non-compliance with guideline-recommended care was primarily attributed to urologists. The patients in the study were elderly, but capable of withstanding these simple measures.
"It wasn't their age, race, ZIP code or how wealthy they were. It all came down to who their doctor was," Chamie said
Dr. Mark S. Litwin, professor of urology and public health and senior author of the study, said it's not clear why physicians are not routinely following established guidelines for care.
"It is puzzling, because strong evidence supports those guidelines," Litwin said. "But this is a wake-up call to all physicians caring for patients with bladder cancer. We know definitively what constitutes high-quality care. Now we just need to make sure it happens."
Patients with primary high-grade bladder cancer, which has not yet invaded the muscle of the bladder, have a 50 to 70 percent chance of their cancer coming back in the bladder following treatment. They also have a 30 to 50 percent chance of the cancer becoming more aggressive and invading into the muscle, where it is much harder to treat. Once the cancer invades the muscle, the bladder and surrounding organs must be removed and both the quality and the quantity of the patient's life are significantly impacted, Chamie said.
Chamie said that, at diagnosis, about 75 percent of bladder patients have disease that has not invaded the muscle. So treating those patients with the guideline-recommended care to help minimize recurrences and prevent invasion of the tumor into the muscle could help a large number of patients.
The recommended medical guidelines call for injecting a cancer-killing drug directly into the bladder to minimize recurrence and progression. They also recommend an intense follow-up schedule, including the repeated use of a scope to evaluate the bladder from the inside, a procedure called cystoscopy, and a urine test that is similar to a pap smear every three months to check for abnormal cells.
Only one patient in the study, which analyzed date from Surveillance, Epidemiology and End Results (SEER)-Medicare linked database, was given the recommended care. The study also found that nearly half of urologists treating these patients had not performed at least one cystoscopy, one urine test, and one infusion of the cancer-killing drug into the bladder.
To rectify the situation, Chamie and Litwin suggest a quality-improvement initiative and or changes to physician reimbursements. To complicate matters, despite the poor compliance rate, bladder cancer is the most expensive malignancy to treat on a per-patient level. While improving compliance with changes to physician reimbursement or a quality improvement initiative will increase healthcare costs in the short term, preventing recurrences or progression of the cancer likely will cut costs in the long term.
"We have to improve compliance and there are two ways to do that: Modify our reimbursement schedules to provide incentives to doctors to follow the guidelines, or go out and interact and educate the community urologists - who are delivering the vast majority of bladder cancer care - on the importance of providing compliant care," Chamie said. "Unlike some patients diagnosed with bladder cancer after having it spread to other sites when it's too late to treat effectively, or those with low-grade tumors that are not likely to ever be aggressive, this is a potentially curable cohort of patients. If we don't do a good enough job treating these cancers, we're going to lose these patients."
Wednesday, June 29, 2011
MAKE BLADDER CANCER CELLS MORE SUSCEPTIBLE TO CHEMOTHERAPY
Ω
Improving efficacy of drugs would boost post-surgery survivorship
Researchers at the UC Davis Cancer Center have discovered a way of sensitizing muscle-invasive bladder cancer cells so that they succumb to the toxic effects of chemotherapy. The finding adds to mounting evidence that tiny strands of RNA — called microRNA — play key roles in some of the deadliest types of cancer.
In the current study, published online June 28 in International Journal of Cancer, researchers boosted the production of a microRNA found in bladder cancer cell lines — encoded for by the gene miR-34a — and found that this resulted in more of the cells being killed by cisplatin, a chemotherapy drug used to treat many types of cancer.
Ralph deVere White
"When we took the bladder cancer cell lines and activated miR-34a, they were more responsive to chemotherapy," said Ralph deVere White, UC Davis Cancer Center director and professor of urology.
The study establishes, for the first time, a link between sensitivity of bladder cancer cells to chemotherapy and the expression of miR-34a. It suggests that miR-34a may be used as a predictor of response to chemotherapy, as well as a target for new drugs.
Currently, about 50 percent of patients with advanced bladder cancer will survive five years after diagnosis. Although clinical trials have demonstrated that chemotherapy before surgery can improve survival rates, it is rarely used because fewer than 50 percent of patients will respond favorably. Without knowing which patients will improve as a result of chemotherapy, physicians are generally reluctant to use a treatment that can cause their patients to suffer significant side effects.
"So, now we have to prove that it works to predict chemotherapy response in patients," deVere White said. To that end, UC Davis has entered into a partnership with Israel-based Rosetta Genomics to develop a microRNA profile for muscle-invasive bladder cancer that may be used to predict response to chemotherapy.
As part of the current study, deVere White and his colleagues studied 27 patients and found that many who expressed lower levels of miR-34a subsequently did not respond to the combined chemotherapy-surgery treatment. Because the finding was not statistically significant, however, further work in this area is needed.
The team also studied tumor samples taken from eight of the patients who did not respond to chemotherapy. They compared the expression of miR-34a before and after chemotherapy.
"We wanted to see, if you looked at the patient's tissue before chemotherapy, were there differentially expressed microRNAs in the patients who responded to the drugs versus those that didn't respond," deVere White explained.
The team found that expression of miR-34a increased after treatment in only two of the eight cases, suggesting that gene expression levels remained low during treatment and confirming the link between low gene expression and failure to respond to treatment.
"The combined data indicate that the elevation of miR-34a expression levels prior to chemotherapy would be of benefit to muscle-invasive bladder cancer patients, particularly in a setting of low mi-R-34a expression," the authors write.
Since their discovery in 1993, microRNAs have been found to be involved in a number of types of cancer, heart disease and diseases of the nervous system. In 2007, deVere White was part of a team that identified miR-125b, a gene that encodes for a microRNA that jump starts prostate cancer cell growth midway through the disease process, eventually causing it to become fatal.
The microRNA studied here was also recently found to play a role in medulloblastoma, an aggressive type of brain cancer. MicroRNAs, which are usually 22 to 33 nucleotides in length, are known as post-transcriptional regulators. That means they work by turning genes on or off during the part of the protein synthesis process that involves making a strand of RNA from a DNA template. The human genome encodes for an estimated 1,000 microRNAs.
According to the authors, future studies involving miR-34a will focus on testing its ability to increase sensitivity to chemotherapy and analysis of miR-34a expression in patients with muscle-invasive bladder cancer. With the currently low chemotherapy success rate and poor five-year survival rate for patients with this disease, "such studies are clearly warranted," the authors write.
"If we can prove what is causing chemotherapy resistance in patients with muscle-invasive bladder cancer, American ingenuity will come up with ways to overcome it," predicted deVere White.
Improving efficacy of drugs would boost post-surgery survivorship
Researchers at the UC Davis Cancer Center have discovered a way of sensitizing muscle-invasive bladder cancer cells so that they succumb to the toxic effects of chemotherapy. The finding adds to mounting evidence that tiny strands of RNA — called microRNA — play key roles in some of the deadliest types of cancer.
In the current study, published online June 28 in International Journal of Cancer, researchers boosted the production of a microRNA found in bladder cancer cell lines — encoded for by the gene miR-34a — and found that this resulted in more of the cells being killed by cisplatin, a chemotherapy drug used to treat many types of cancer.
Ralph deVere White
"When we took the bladder cancer cell lines and activated miR-34a, they were more responsive to chemotherapy," said Ralph deVere White, UC Davis Cancer Center director and professor of urology.
The study establishes, for the first time, a link between sensitivity of bladder cancer cells to chemotherapy and the expression of miR-34a. It suggests that miR-34a may be used as a predictor of response to chemotherapy, as well as a target for new drugs.
Currently, about 50 percent of patients with advanced bladder cancer will survive five years after diagnosis. Although clinical trials have demonstrated that chemotherapy before surgery can improve survival rates, it is rarely used because fewer than 50 percent of patients will respond favorably. Without knowing which patients will improve as a result of chemotherapy, physicians are generally reluctant to use a treatment that can cause their patients to suffer significant side effects.
"So, now we have to prove that it works to predict chemotherapy response in patients," deVere White said. To that end, UC Davis has entered into a partnership with Israel-based Rosetta Genomics to develop a microRNA profile for muscle-invasive bladder cancer that may be used to predict response to chemotherapy.
As part of the current study, deVere White and his colleagues studied 27 patients and found that many who expressed lower levels of miR-34a subsequently did not respond to the combined chemotherapy-surgery treatment. Because the finding was not statistically significant, however, further work in this area is needed.
The team also studied tumor samples taken from eight of the patients who did not respond to chemotherapy. They compared the expression of miR-34a before and after chemotherapy.
"We wanted to see, if you looked at the patient's tissue before chemotherapy, were there differentially expressed microRNAs in the patients who responded to the drugs versus those that didn't respond," deVere White explained.
The team found that expression of miR-34a increased after treatment in only two of the eight cases, suggesting that gene expression levels remained low during treatment and confirming the link between low gene expression and failure to respond to treatment.
"The combined data indicate that the elevation of miR-34a expression levels prior to chemotherapy would be of benefit to muscle-invasive bladder cancer patients, particularly in a setting of low mi-R-34a expression," the authors write.
Since their discovery in 1993, microRNAs have been found to be involved in a number of types of cancer, heart disease and diseases of the nervous system. In 2007, deVere White was part of a team that identified miR-125b, a gene that encodes for a microRNA that jump starts prostate cancer cell growth midway through the disease process, eventually causing it to become fatal.
The microRNA studied here was also recently found to play a role in medulloblastoma, an aggressive type of brain cancer. MicroRNAs, which are usually 22 to 33 nucleotides in length, are known as post-transcriptional regulators. That means they work by turning genes on or off during the part of the protein synthesis process that involves making a strand of RNA from a DNA template. The human genome encodes for an estimated 1,000 microRNAs.
According to the authors, future studies involving miR-34a will focus on testing its ability to increase sensitivity to chemotherapy and analysis of miR-34a expression in patients with muscle-invasive bladder cancer. With the currently low chemotherapy success rate and poor five-year survival rate for patients with this disease, "such studies are clearly warranted," the authors write.
"If we can prove what is causing chemotherapy resistance in patients with muscle-invasive bladder cancer, American ingenuity will come up with ways to overcome it," predicted deVere White.
Friday, June 24, 2011
Smokers With Prostate Cancer Have Higher Death Risk
A just-released study about smoking and prostate cancer gives men one more reason to quit. The study says that smokers who are diagnosed with prostate cancer may have an increased risk of dying from the disease compared to non-smokers. They also have an increased risk of the cancer coming back.
Researchers from the Harvard School of Public Health, Boston studied 5,366 men diagnosed with prostate cancer between 1986 and 2006. Five years after diagnosis, 94.8% of men who had never smoked had not died of their prostate cancer, compared with 91.7% of current smokers.
The study, called "Smoking and Prostate Cancer Survival and Recurrence, is published in the June 22/29 issue of the Journal of the American Medical Association.
Durado D. Brooks, MD, American Cancer Society director of prostate and colorectal cancer, says this study is significant because it’s the largest study of its kind to show links between smoking and the likelihood of dying from prostate cancer.
It also takes into account several factors associated with negative outcomes of prostate cancer, including Gleason score (a measure of how likely the cancer is to grow quickly) and the stage of cancer at diagnosis. Previous studies have shown a link between smoking and being diagnosed at a later stage, and the new study accounted for that.
Brooks says this suggests something about cigarettes themselves, and not just the men’s behavior, is causing the increased risk of prostate cancer death.
The study also showed that men who had quit smoking at least 10 years before their diagnosis had prostate cancer death risks similar to men who had never smoked. Brooks says this means it’s never too late to quit. "Never smoke. Don’t start. If you smoke, quit now. It’s never too late."
Researchers from the Harvard School of Public Health, Boston studied 5,366 men diagnosed with prostate cancer between 1986 and 2006. Five years after diagnosis, 94.8% of men who had never smoked had not died of their prostate cancer, compared with 91.7% of current smokers.
The study, called "Smoking and Prostate Cancer Survival and Recurrence, is published in the June 22/29 issue of the Journal of the American Medical Association.
Durado D. Brooks, MD, American Cancer Society director of prostate and colorectal cancer, says this study is significant because it’s the largest study of its kind to show links between smoking and the likelihood of dying from prostate cancer.
It also takes into account several factors associated with negative outcomes of prostate cancer, including Gleason score (a measure of how likely the cancer is to grow quickly) and the stage of cancer at diagnosis. Previous studies have shown a link between smoking and being diagnosed at a later stage, and the new study accounted for that.
Brooks says this suggests something about cigarettes themselves, and not just the men’s behavior, is causing the increased risk of prostate cancer death.
The study also showed that men who had quit smoking at least 10 years before their diagnosis had prostate cancer death risks similar to men who had never smoked. Brooks says this means it’s never too late to quit. "Never smoke. Don’t start. If you smoke, quit now. It’s never too late."
Saturday, June 4, 2011
Study links acetaminophen to lower prostate cancer risk
A new study from American Cancer Society researchers finds use of 30 tablets a month or more of acetaminophen (Anacin)for five or more years was associated with an estimated 38% lower risk of prostate cancer. The study appears in Cancer Epidemiology, Biomarkers and Prevention and is one of only two studies of prostate cancer to date that have examined the association with acetaminophen use that was both long-term and regular.
Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), particularly long-term use, has been associated with modestly reduced risk of prostate cancer in some previous epidemiologic studies. Acetaminophen, a commonly used pain-reliever, is not traditionally considered an NSAID but can have anti-inflammatory effects.
For the current study, researchers led by Eric Jacobs, Ph.D., American Cancer Society epidemiologist, examined the association between acetaminophen use and prostate cancer incidence among 78,485 men in the Cancer Prevention Study II Nutrition Cohort. Information on acetaminophen use was obtained from a questionnaire completed at study enrollment in 1992 and updated using follow-up questionnaires in 1997 and every two years thereafter.
During follow-up from 1992 through 2007, there were 8,092 incident prostate cancer cases identified. Current regular use of acetaminophen (> 30 pills per month) for 5 years or more was associated with lower risk of overall prostate cancer (RR = 0.62, 95% CI 0.44-0.87) as well as lower risk of aggressive prostate cancer (RR = 0.49, 95% CI 0.27-0.88). Current regular use of < 5 years duration was not associated with prostate cancer risk.
"While the results of this observational study suggest that long-term regular acetaminophen use may be associated with lower prostate cancer risk, our findings require replication by other studies, and do not justify use of acetaminophen to prevent prostate cancer. Acetaminophen is considered relatively safe when used at recommended doses but unintentional acetaminophen overdose is an important cause of acute liver failure." said Dr. Jacobs. "Still, results of this study could lead to further research on acetaminophen that might provide biological insights about the process of prostate cancer development and how this process could be slowed."
Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), particularly long-term use, has been associated with modestly reduced risk of prostate cancer in some previous epidemiologic studies. Acetaminophen, a commonly used pain-reliever, is not traditionally considered an NSAID but can have anti-inflammatory effects.
For the current study, researchers led by Eric Jacobs, Ph.D., American Cancer Society epidemiologist, examined the association between acetaminophen use and prostate cancer incidence among 78,485 men in the Cancer Prevention Study II Nutrition Cohort. Information on acetaminophen use was obtained from a questionnaire completed at study enrollment in 1992 and updated using follow-up questionnaires in 1997 and every two years thereafter.
During follow-up from 1992 through 2007, there were 8,092 incident prostate cancer cases identified. Current regular use of acetaminophen (> 30 pills per month) for 5 years or more was associated with lower risk of overall prostate cancer (RR = 0.62, 95% CI 0.44-0.87) as well as lower risk of aggressive prostate cancer (RR = 0.49, 95% CI 0.27-0.88). Current regular use of < 5 years duration was not associated with prostate cancer risk.
"While the results of this observational study suggest that long-term regular acetaminophen use may be associated with lower prostate cancer risk, our findings require replication by other studies, and do not justify use of acetaminophen to prevent prostate cancer. Acetaminophen is considered relatively safe when used at recommended doses but unintentional acetaminophen overdose is an important cause of acute liver failure." said Dr. Jacobs. "Still, results of this study could lead to further research on acetaminophen that might provide biological insights about the process of prostate cancer development and how this process could be slowed."
Half of Prostate Cancers Could Potentially Benefit from New Type of Cancer Drugs
About half of prostate cancers have a genetic anomaly that appears to make tumor cells responsive to a new class of cancer-fighting drugs, a new study from the University of Michigan Comprehensive Cancer Center finds.
The drugs, called PARP inhibitors, are currently being tested in breast cancer patients with mutations in the BRCA1 and BRCA2 genes, which are found in up to 10 percent of all breast cancers.
Half of prostate cancers have a genomic rearrangement that causes the fusion of two genes called TMPRSS2 and ERG. This gene fusion, believed to be the triggering event of prostate cancer, was initially discovered in 2005 by U-M researchers led by Arul Chinnaiyan, M.D., Ph.D.
“This type of gene fusion occurs in about 50 percent of prostate cancers, but the genes involved have been notoriously difficult to target therapeutically. We found that instead of targeting the gene fusion product directly, we could block the function of critical interacting partners, such as PARP1,” says Chinnaiyan, a Howard Hughes Medical Institute researcher, director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at the U-M Medical School.
Chinnaiyan is the senior author of the current study, which appears in the May 17 issue of Cancer Cell.
“Our studies suggest that the total population of patients who could benefit from PARP inhibition could be significantly expanded,” says Chad Brenner, Ph.D. candidate at U-M, who is the first author on the study.
Working with prostate cancer models in cell lines and mice, researchers found that therapies using the PARP inhibitor Olaparib helped shrink tumors expressing the TMPRSS2:ERG gene fusion and blocked the ability of tumors to spread. Olaparib had no effect on tumors that did not have the gene fusion.
PARP inhibitors are not currently approved by the U.S. Food and Drug Administration, but initial trials in breast cancer patients indicate they can be administered safely and are well-tolerated.
Prostate cancer statistics: 217,730 Americans will be diagnosed with prostate cancer this year and 32,050 will die from the disease, according to the American Cancer Society.
Reference: Cancer Cell, Vol. 19, No. 5, pp. 664-678, May 17, 2011
The drugs, called PARP inhibitors, are currently being tested in breast cancer patients with mutations in the BRCA1 and BRCA2 genes, which are found in up to 10 percent of all breast cancers.
Half of prostate cancers have a genomic rearrangement that causes the fusion of two genes called TMPRSS2 and ERG. This gene fusion, believed to be the triggering event of prostate cancer, was initially discovered in 2005 by U-M researchers led by Arul Chinnaiyan, M.D., Ph.D.
“This type of gene fusion occurs in about 50 percent of prostate cancers, but the genes involved have been notoriously difficult to target therapeutically. We found that instead of targeting the gene fusion product directly, we could block the function of critical interacting partners, such as PARP1,” says Chinnaiyan, a Howard Hughes Medical Institute researcher, director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at the U-M Medical School.
Chinnaiyan is the senior author of the current study, which appears in the May 17 issue of Cancer Cell.
“Our studies suggest that the total population of patients who could benefit from PARP inhibition could be significantly expanded,” says Chad Brenner, Ph.D. candidate at U-M, who is the first author on the study.
Working with prostate cancer models in cell lines and mice, researchers found that therapies using the PARP inhibitor Olaparib helped shrink tumors expressing the TMPRSS2:ERG gene fusion and blocked the ability of tumors to spread. Olaparib had no effect on tumors that did not have the gene fusion.
PARP inhibitors are not currently approved by the U.S. Food and Drug Administration, but initial trials in breast cancer patients indicate they can be administered safely and are well-tolerated.
Prostate cancer statistics: 217,730 Americans will be diagnosed with prostate cancer this year and 32,050 will die from the disease, according to the American Cancer Society.
Reference: Cancer Cell, Vol. 19, No. 5, pp. 664-678, May 17, 2011
Rising PSA means prostate cancer is in patient's future
New study defuses controversy, shows why individual patient trends are critical
A man's rising PSA (prostate-specific antigen) level over several years – which had been seen as a possible warning sign of prostate cancer – has recently come under fire as a screening test because it sometimes prompts biopsies that turn out to be normal.
A new study, however, shows nearly 70 percent of men who had rising PSA levels and subsequent normal biopsies were eventually diagnosed with prostate cancer, according to research from Northwestern University Feinberg School of Medicine. The trend of a PSA level over several years is called PSA velocity.
"Our findings show an elevated and rising PSA level or velocity should lead a clinician to follow a patient more closely, even if he has a negative biopsy," said lead investigator William Catalona, M.D., director of the clinical prostate cancer program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "One negative biopsy isn't the end of the road."
The findings were presented May 18 at the American Urological Association 2011 Annual Meeting. Catalona is a professor of urology at the Feinberg School and a urologist at Northwestern Memorial Hospital.
PSA is a substance whose elevated levels can indicate prostate cancer but can also be caused by prostate inflammation or enlargement or other conditions. Catalona, known as the father of the PSA screening, was the first to show in 1991 that a simple blood test measuring PSA levels could be used to detect prostate cancer.
For the study, Northwestern researchers looked in their database at the history of 97 patients with a rising PSA trend (or velocity) who had a subsequent negative biopsy. Researchers found 66 percent of patients were eventually diagnosed with prostate cancer, 20 percent had a benign prostate, 8 percent had protatitis and 6 percent had premalignant lesions.
"This underscores the importance of using a patient's individual PSA trend when deciding whether to pursue a prostate biopsy," said co-investigator Gregory Auffenberg, M.D., a resident in urology at the Feinberg School. "It's not enough to only look at an individual PSA value when historical data is also available."
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