April, 2013

One Disease, Two Mechanisms: Genetic Root to Early-Onset Prostate Cancer Identified

13th February 2013 While prostate cancer is the most common cancer in elderly Western men it also, but more rarely, strikes patients aged between 35 and 50. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, in collaboration with several other research teams in Germany*, have discovered that such early-onset prostate cancers are triggered by a different mechanism from that which causes the disease at a later age. Their findings are published February 11 in Cancer Cell, and might have important consequences for the diagnosis and treatment of prostate cancer in younger patients. The researchers compared the genomes of 11 early-onset tumours with 7 late-onset tumours and observed marked differences at the molecular level. The genomes of early-onset prostate tumours undergo a relatively small number of changes compared to tumours that develop in older patients. However, this small number of events leads to crucial exchanges of DNA between chromosomes, causing genes that are normally independent to become tightly linked (known as ‘fusion genes’). Many of the genes affected by these rearrangements are usually activated by androgen hormones, such as testosterone. Through these rearrangements they become connected to cancer genes, resulting in fusion genes that can be activated by androgen hormones, so that otherwise inactive genes with the potential to cause cancer are now switched on. “Prostate cancer in young patients appears to be specifically triggered by androgens and to involve genetic alterations that distinguish this cancer from prostate tumours in older patients,” explains Jan Korbel, who led the study at EMBL. “We also measured the levels of androgen receptors in a large cohort of patients from Hamburg, and found data consistent with our initial genomic analysis.” Younger patients with prostate cancer tend to have higher levels of androgen hormone receptors than older patients with the same disease. This could be a natural effect, because the level of these hormones decreases in men older than 50. But it supports the researchers’ conclusion that androgens might trigger the mechanism leading to prostate cancer in younger patients, and not in older ones. Further research is needed to provide the scientific and medical community with more details, particularly regarding the medical impact of testosterone levels in men. However, in the future these findings may have widespread clinical consequences. “We hope that our findings on the cause of the disease will promote the development of new strategies to diagnose, prevent, and even...

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Emotional Stress Reduces Effectiveness of Prostate Cancer Therapies in Animal Model

January 25th 2013 Not surprisingly, a cancer diagnosis creates stress. And patients with prostate cancer show higher levels of anxiety compared to other cancer patients. A new study by researchers at Wake Forest Baptist Medical Center indicates that stress is not just an emotional side effect of the diagnosis; it also can reduce the effectiveness of prostate cancer drugs and accelerate the development of prostate cancer. The findings are published in the February issue of the Journal of Clinical Investigation. The Wake Forest Baptist team, headed by George Kulik, D.V.M., Ph.D., associate professor of cancer biology, tested the effects of behavioral stress in two different mouse models of prostate cancer. One model used mice that were implanted with human prostate cancer cells and treated with a drug that is currently in clinical trial for prostate cancer treatment. When the mice were kept calm and free of stress, the drug destroyed prostate cancer cells and inhibited tumor growth. However, when the mice were stressed, the cancer cells didn’t die and the drug did not inhibit tumor growth. In the second model, mice genetically modified to develop prostate cancer were used. When these mice were repeatedly stressed, the size of prostate tumors increased. When the mice were treated with bicalutamide, a drug currently used to treat prostate cancer, their prostate tumors decreased in size. However, if mice were subjected to repeated stress, the prostate tumors didn’t respond as well to the drug. After analyzing the data, the Wake Forest Baptist researchers identified the cell signaling pathway by which epinephrine, a hormone also known as adrenaline, sets off the cellular chain reaction that controls cell death. Considering that prostate cancer diagnosis increases stress and anxiety levels, stress-induced activation of the signaling pathway that turns off the cell death process may lead to a vicious cycle of stress and cancer progression, Kulik said. Yet in both models in which the mice were given beta-blocker, stress did not promote prostate tumor growth. Beta-blocker is a drug that inhibits the activation of anti-death signaling by epinephrine. “Providing beta-blockers to prostate cancer patients who had increased epinephrine levels could improve the effectiveness of anti-cancer therapies,” Kulik said. “Our findings could be used to identify prostate cancer patients who will benefit from stress reduction or from pharmacological inhibition of stress-inducing signaling.” The researchers now plan to test the same signaling mechanism that was identified in mice to...

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