Archive for the ‘Urology’ Category

Newest precision medicine tool: Prostate cancer organoids

The researchers, whose results were published today in Cell, successfully grew six prostate cancer organoids from biopsies of patients with metastatic prostate cancer and a seventh organoid from a patient’s circulating tumor cells. Organoids are three-dimensional structures composed of cells that are grouped together and spatially organized like an organ. The histology, or tissue structure, of the prostate cancer organoids is highly similar to the metastasis sample from which they came. Sequencing of the metastasis samples and the matched organoids showed that each organoid is genetically identical to the patient’s cancer from which it originated.

“Identifying the molecular biomarkers that indicate whether a drug will work or why a drug stops working is paramount for the precision treatment of cancer,” said Yu Chen, MD, PhD, Assistant Attending Physician in the Genitourinary Oncology Service and Human Oncology and Pathogenesis Program at MSK. “But we are limited in our capacity to test drugs — especially in the prostate cancer setting, where only a handful of prostate cancer cell lines are available to researchers.”

With the addition of the seven prostate cancer organoids described in the Cell paper, Dr. Chen’s team has effectively doubled the number of existing prostate cancer cell lines.

“We now have a new resource at our disposal that captures the molecular diversity of prostate cancer. This will be an invaluable tool we can use to test drug sensitivity,” he added.

The use of organoids in studying cancer is relatively new, but the field is exploding quickly according to Dr. Chen. In 2009, Hans Clevers, MD, PhD, of the Hubrecht Institute in the Netherlands demonstrated that intestinal stem cells could form organoids. Dr. Clevers is the lead author on a companion piece also published in Cell today that describes how to create healthy prostate organoids. Dr. Chen’s paper is the first to demonstrate that organoids can be grown from prostate cancer samples.

The prostate cancer organoids can be used to test multiple drugs simultaneously, and Dr. Chen’s team is already retrospectively comparing the drugs given to each patient against the organoids for clues about why the patient did or didn’t respond to therapy. In the future, it’s possible that drugs could be tested on a patient’s organoid before being given to the patient to truly personalize treatment.

After skin cancer, prostate cancer is the most common cancer in American men — about 233,000 new cases will be diagnosed in 2014. It is also the second leading cause of cancer death in men; 1 in 36 men will die of the disease.

Despite its prevalence, prostate cancer has been difficult to replicate in the lab. Many mutations that play a role in its growth are not represented in the cell lines currently available. Cell lines can also differ from their original source, and because they are composed of single cells, they do not offer the robust information that an organoid — which more closely resembles a living organ — can provide.

source : http://www.sciencedaily.com/releases/2014/09/140904131142.htm

Blood test for ‘nicked’ protein predicts prostate cancer treatment response

The study evaluated two groups of 31 men with prostate cancer that had spread and whose blood levels of prostate-specific antigen (PSA) were still rising despite low testosterone levels. Investigators gave each man either enzalutamide (Xtandi) or abiraterone (Zytiga) and tracked whether their PSA levels continued to rise, an indication that the drugs were not working. In the enzalutamide group, none of 12 patients whose blood samples tested positive for AR-V7 responded to the drug, compared with 10 responders among 19 men who had no AR-V7 detected. In the abiraterone group, none of six AR-V7-positive patients responded, compared with 17 responders among 25 patients lacking AR-V7.

Enzalutamide and abiraterone have been very successful in lengthening the lives of about 80 percent of patients with metastatic prostate cancer, says Emmanuel Antonarakis, M.D., assistant professor of oncology at Johns Hopkins, but the drugs do not work in the remaining 20 percent of patients.

“Until now, we haven’t been able to predict which patients will not respond to these therapies. If our results are confirmed by other researchers, a blood test could use AR-V7 as a biomarker to predict enzalutamide and abiraterone resistance, and let us direct patients who test positive for AR-V7 toward other types of therapy sooner, saving time and money while avoiding futile therapy,” says Antonarakis.

Prostate cancer thrives on male sex hormones (or “androgens”), including testosterone. Enzalutamide and abiraterone target proteins called androgen receptors and block the receptors’ ability to activate prostate cancer cells. AR-V7 is a shortened form of the androgen receptor that lacks a binding spot targeted by enzalutamide and abiraterone. With no binding spot for the two drugs, AR-V7 is free to manipulate prostate cancer cells’ genetic material, which makes the cancer cells grow and spread.

Antonarakis and his colleague Jun Luo, Ph.D., who first identified AR-V7 in 2008, also tracked patients’ progression-free survival (the length of time a patient lives with the disease but does not get worse) and overall survival. They found that, in men receiving enzalutamide, progression-free survival was 2.1 months in AR-V7-positive patients and 6.1 months in AR-V7-negative patients, while overall survival was 5.5 months in AR-V7-positive men and up to 9 months in AR-V7-negative men. Similarly, in men receiving abiraterone, progression-free survival was 2.3 months in AR-V7-positive patients and up to 6 months in AR-V7-negative patients, while overall survival was 10.6 months in AR-V7-positive men and up to 12 months in AR-V7-negative men. The investigators caution that most of the study patients had advanced disease and received multiple prior therapies, so their outcomes may not be generalizable to all men with prostate cancer.

“Patients whose blood samples contained AR-V7 got no benefit from either enzalutamide or abiraterone,” says Antonarakis. He adds that the shortened AR-V7 protein could appear in patients’ blood samples at the very start of therapy or acquired later, after therapy has begun. He says, “This test could be used before starting enzalutamide or abiraterone therapy, and if the test shows the presence of AR-V7, patients may opt for a different therapy. It could also be used to monitor patients receiving enzalutamide or abiraterone for AR-V7, providing an indication these drugs may not work for much longer.”

source : http://www.sciencedaily.com/releases/2014/09/140903203752.htm

New method for non-invasive prostate cancer screening

Now a team of researchers led by Shaoxin Li at Guangdong Medical College in China has demonstrated the potential of a new, non-invasive method to screen for prostate cancer, a common type of cancer in men worldwide. They describe their laboratory success testing an existing spectroscopy technique called surface-enhanced Raman scattering (SERS) with a new, sophisticated analysis technique called support vector machine (SVM).

As they described in a new paper in Applied Physics Letters, from AIP Publishing, they combined SERS and SVM and applied them to blood samples collected from 68 healthy volunteers and 93 people who were clinically confirmed to have prostate cancer. They found their technique could identify the cases of cancer with an accuracy of 98.1 percent.

If the technique proves safe and effective in clinical trials, it may become a new method available to patients and their doctors, helping to improve the early detection and diagnosis of this type of cancer, said Li.

“The results demonstrate that label-free serum SERS analysis combined with SVM diagnostic algorithm has great potential for non-invasive prostate cancer screening,” said Li. “Compared to traditional screening methods, this method has the advantages of being non-invasive, highly sensitive and very simple for prostate cancer screening.”

A COMMON CAUSE OF CANCER

According to the World Health Organization, prostate cancer is one of the most common types of cancer in men worldwide and a leading cause of cancer-related death. Every year, there are about 899,000 new cases and 260,000 mortalities, comprising 6 percent of all cancer deaths globally. About 1 in every 6 men will develop prostate cancer over their lifetimes.

While a simple blood test for elevated levels of a protein marker known as prostate specific antigen (PSA) has been used for years to screen for early cases of prostate cancer, the test is far from perfect because the elevated PSA levels can be caused by many things unrelated to cancer. This contributes to over-diagnosis, uncomfortable tissue biopsies and other unnecessary treatment, which can be costly and carry significant side effects. Because of this, the U.S. Preventative Services Task Force now recommends against PSA-based screening for prostate cancer.

According to Li, many scientists have thought about applying SERS to cancer detection because the surface-sensitive type of spectroscopy has been around for years and is sensitive enough to identify key molecules in very low abundance, like pesticide residues on a contaminated surface. This would seem to make it perfect for spotting subtle signals of DNA, proteins or fatty molecules that would mark a case of cancer — exactly why he and his team tackled the problem.

The challenge, he said, was that these changes were, if anything, too subtle. The signal differences between the serum samples taken from the 68 healthy volunteers and the 93 people with prostate cancer were too tiny to detect. So to accurately distinguish between these samples, Li’s group employed a powerful spectral data processing algorithm, support vector machine (SVM), which effectively showed the difference.

While the work is preliminary, it shows that serum SERS spectroscopy combined with SVM diagnostic algorithm has the potential to be a new method for non-invasive prostate cancer screening, Li said. The next research step, he added, is to refine the method and explore whether this method can distinguish cancer staging.

source : http://www.sciencedaily.com/releases/2014/09/140902114041.htm