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A Nine-gene Signature Identified for Aggressive Prostate Cancers

David Olmos, Johann de Bono, first and senior authors respectively, Lancet Oct 2012—Study funded in part by PCF

October 09, 2012 -- There are many forms of prostate cancer; some indolent and slow-growing, others lethal and aggressive. Current testing allows doctors to stratify patients diagnosed with prostate cancer into either the former or latter groups, but with imperfect accuracy. To improve accuracy, scientists are actively searching for biological markers that improve doctors’ ability to accurately predict each man’s risk of having an aggressive or indolent form of disease, once he is diagnosed with prostate cancer. In addition, even men who are diagnosed with an advanced form of prostate cancer--known as treatment-resistant prostate cancer, or castration-resistant prostate cancer (CRPC) due to these tumor’s resistance to drugs that lower levels of male hormone in the body--have highly variable survival times, ranging from months to a decade or more.

This week, a study published in Lancet Oncology, identifies a nine-gene signature that was predictive of overall survival in men with treatment-resistant prostate cancer. Men whose blood tested positive for this gene signature had overall survival times that were approximately one year shorter than men who lacked the signature.

"This very interesting blood test, if verified in additional independent patient cohorts, can provide important prognostic information to guide patient treatment and better stratification of patients for clinical trials for new treatments in CRPC," says Dr. Howard Soule, chief science officer at the Prostate Cancer Foundation.

In the first phase of the study, the researchers (several of whom are PCF-funded investigators) scanned blood samples from 100 men in the U.K. with prostate cancer—69 with advanced, treatment-resistant cancers, and 31 men deemed to have low-risk disease. Based upon their unique gene expression patterns (which genes are working at what level of capacity) the men were placed into four distinct sub-groups. After following the men for 2.5 years, the researchers found that men in one particular subgroup had lower survival rates than those in the other three groups—10.7 months and 25.6 months respectively.

In the second phase of the study, 70 additional men with treatment-resistant prostate cancer from the U.S. had their blood samples assessed in order to validate the phase one findings. And, as in the first phase of the study, men in the subgroup with the nine-gene signature had significantly shorter survival times—9.2 months compared to 21.6 months for men lacking the signature.

In their paper and also at the presentation of their data earlier this month at the annual meeting of the European Society for Medical Oncologists in Vienna, the study authors noted that using whole blood to test for a gene signature is vastly easier than using tumor tissue, which is hard to access, especially once the prostate gland has been surgically removed and cancer sites have spread to bone, as is often the case in advanced forms of prostate cancer.

The authors write in the study that their “results suggest that whole-blood gene profiling could identify gene expression signatures that stratify patients with [treatment-resistant prostate cancer] into very distinct prognosis groups.” They also suggested that their gene signature may prove useful as an extra sensitive marker of early spread of prostate cancer to bone, which could allow doctors to begin certain chemotherapies earlier, but that more study would be needed to validate this point.

PCF-funded investigators involved in the Lancet Oncology study include Gerhardt Attard, MD, Charles Drake, MD, Howard Scher, MD and Johann de Bono, MD. The Prostate Cancer Foundation received recognition as a financial contributor for the study, both in the publication and at the European Society for Medical Oncology (ESMO) conference in Vienna, Austria.

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