New study below [1] [2].
"Whole blood samples from a prospective biorepository of 85 mCRPC patients before treatment initiation with abiraterone (n=56) or enzalutamide (n=29) were analyzed via droplet digital polymerase chain reaction."
"High AR-V7 expression levels in whole blood were detectable in 18% (15/85) of patients. No patient with high AR-V7 expression achieved a PSA response, and AR-V7 status was an independent predictor of PSA response ..."
"Testing of AR-V7 mRNA levels in whole blood is a simple and promising approach to predict poor treatment outcome in mCRPC patients receiving abiraterone or enzalutamide."
...
"Until now, blood tests used to detect prostate tumor cells have looked for specific surface structures on the cells. It’s not only a time-consuming and expensive process because of the special equipment required for the tests, but it’s also not always efficacious. If the cells being tested lack the specific structure being searched for, these tests fail to detect their presence. The new test developed by TUM researchers utilizes a completely different method in order to reliably, quickly and inexpensively measure the presence of the modified receptor AR-V7 at an early stage. Moreover, it can also determine whether or not the tumor is resistant to treatment with abiraterone and enzalutamide."
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/288...
Eur Urol. 2017 Aug 14. pii: S0302-2838(17)30653-X. doi: 10.1016/j.eururo.2017.07.024. [Epub ahead of print]
AR-V7 in Peripheral Whole Blood of Patients with Castration-resistant Prostate Cancer: Association with Treatment-specific Outcome Under Abiraterone and Enzalutamide.
Seitz AK1, Thoene S2, Bietenbeck A3, Nawroth R1, Tauber R1, Thalgott M1, Schmid S1, Secci R2, Retz M1, Gschwend JE1, Ruland J2, Winter C4, Heck MM5.
Author information
Abstract
BACKGROUND:
It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide.
OBJECTIVE:
To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients.
DESIGN, SETTING, AND PARTICIPANTS:
Whole blood samples from a prospective biorepository of 85 mCRPC patients before treatment initiation with abiraterone (n=56) or enzalutamide (n=29) were analyzed via droplet digital polymerase chain reaction.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
The association of AR-V7 status with prostate-specific antigen (PSA) response defined by PSA decline ≥50% and with PSA-progression-free survival (PSA-PFS), clinical PFS, and overall survival (OS) was assessed.
RESULTS AND LIMITATIONS:
High AR-V7 expression levels in whole blood were detectable in 18% (15/85) of patients. No patient with high AR-V7 expression achieved a PSA response, and AR-V7 status was an independent predictor of PSA response in multivariable logistic regression analysis (p=0.03). High AR-V7 expression was associated with shorter PSA-PFS (median 2.4 vs 3.7 mo; p<0.001), shorter clinical PFS (median 2.7 vs 5.5 mo; p<0.001), and shorter OS (median 4.0 vs. 13.9 mo; p<0.001). On multivariable Cox regression analysis, high AR-V7 expression remained an independent predictor of shorter PSA-PFS (hazard ratio [HR] 7.0, 95% confidence interval [CI] 2.3-20.7; p<0.001), shorter clinical PFS (HR 2.3, 95% CI 1.1-4.9; p=0.02), and shorter OS (HR 3.0, 95% CI 1.4-6.3; p=0.005).
CONCLUSIONS:
Testing of AR-V7 mRNA levels in whole blood is a simple and promising approach to predict poor treatment outcome in mCRPC patients receiving abiraterone or enzalutamide.
PATIENT SUMMARY:
We established a method for determining AR-V7 status in whole blood. This test predicted treatment resistance in patients with metastatic castration-resistant prostate cancer undergoing treatment with abiraterone or enzalutamide. Prospective validation is needed before application to clinical practice.
Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
KEYWORDS:
Androgen receptor splice variant; Castration-resistant prostate cancer; Droplet digital polymerase chain reaction; Liquid profiling; Resistance
PMID: 28818355 DOI: 10.1016/j.eururo.2017.07.024
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[2] tum.de/en/about-tum/news/pr...
New method predicts therapeutic success of cancer medications
Blood test predicts prostate tumor resistance
22.08.2017, Research news
When bacteria develop antibiotic resistance, treatment with these medications becomes ineffective. Similarly, tumor cells can also change in such a way that renders them resistant to particular medications. This makes it vitally important for cancer patients and their doctors to determine as early as possible whether a specific therapy is working or not. A new blood test developed by researchers at the Technical University of Munich (TUM) can predict drug resistance in patients with advanced prostate cancer.
Prostate cancer tumor cells require the androgen hormone, testosterone, to grow. They possess a receptor to which testosterone binds and then signals the cancer cells to divide and grow. If a prostate tumor has already grown to a large size and started spreading throughout the body, therapeutic drugs are used to block the growth at its molecular origin – either by targeting tumor cell receptors to prevent testosterone from binding, or by entirely blocking the body’s overall production of testosterone. Two of the drugs most frequently used in this type of therapy are abiraterone and enzalutamide.
THE HUNT FOR RESISTANT TUMOR CELLS
During the course of treatment, however, some tumor cells develop resistance to these drugs, and continue to grow and metastasize. The culprit: the tumor’s testosterone receptors have changed their structure, and the new variant can signal the cancer cells to continue dividing and spreading – even without testosterone. The most common receptor variant seen in patients is called AR-V7. “If we know in advance whether or not a tumor has developed cells with this receptor, we can provide advice on an individual basis at an early stage – this can spare seriously-ill patients from undergoing an ineffective therapy,” explains Assistant Professor Dr. Matthias Heck, co-leader of the study and a specialist for Urology at the University Hospital TUM Klinikum rechts der Isar in Munich.
Heck and his team collaborated with colleagues led by Dr. Dr. Christof Winter, a physician and bioinformatician and the head of the “Liquid Profiling and Bioinformatics” lab at the TUM Institute of Clinical Chemistry and Pathobiochemistry, to develop a new blood test. Until now, blood tests used to detect prostate tumor cells have looked for specific surface structures on the cells. It’s not only a time-consuming and expensive process because of the special equipment required for the tests, but it’s also not always efficacious. If the cells being tested lack the specific structure being searched for, these tests fail to detect their presence. The new test developed by TUM researchers utilizes a completely different method in order to reliably, quickly and inexpensively measure the presence of the modified receptor AR-V7 at an early stage. Moreover, it can also determine whether or not the tumor is resistant to treatment with abiraterone and enzalutamide.
HIGH TESTING SENSITIVITY AND ACCURACY
The new blood test provides an alternative to existing models and potential to improve them: It analyzes the amount of AR-V7 RNA molecules in the blood. In each and every one of the cells in our body, RNA is responsible for the translation of genetic information into protein molecules, including receptor molecules. If the test detects high levels of AR-V7 RNA in the blood, it is likely that the patient already has tumor cells resistant to therapy with abiraterone and enzalutamide. Dr. Silvia Thöne, co-lead author of the study, emphasizes the high sensitivity and accuracy of the new testing method: “Only minute amounts of RNA are needed in a sample for the test to work. Additionally, since AR-V7 RNA is present in every tumor cell that possesses the resistant receptors, it means that no tumor cells are slipping by undetected.”
For the study, TUM researchers analyzed blood samples from 85 patients with advanced stages of prostate cancer. They were able to successfully demonstrate that approximately one fifth of the patients had large amounts of AR-V7 RNA in their blood – an indication of large quantities of resistant tumor cells. It was exactly these patients who failed to respond to therapy with abiraterone and enzalutamide. They also had poorer prognoses during the subsequent course of their illness: Their tumors returned more quickly and they had shorter survival times than other patients.
MORE WORK AHEAD
“We were able to demonstrate that we can accurately predict whether or not resistance against abiraterone or enzalutamide is present in a patient,” explains Winter. The next step for researchers will be to further improve upon the testing method and also compare its efficacy to that of existing testing methods using a larger sample of patients. The goal? TUM researchers want to determine if their new blood test can be incorporated into the routine battery of clinical examinations for prostate cancer patients in the future.
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The study was conducted in collaboration with the German Cancer Consortium (DKTK). Christof Winter and Silvia Thöne are among the experts at the DKTK who are driving the ongoing development of liquid biopsies with Germany's leading oncology centers.
ORIGINAL PUBLICATION:
A. K. Seitz, S. Thoene, A. Bietenbeck, R. Nawroth, R. Tauber, M. Thalgott, S. Schmid, R. Secci, M. Retz, J. E. Gschwend, J. Ruland, C. Winter, M. M. Heck, AR-V7 in peripheral whole blood of castration-resistant prostate cancer patients: association with treatment-specific outcome under abiraterone and enzalutamide, European Urology, 14 August 2017, DOI: 10.1016/j.eururo.2017.07.024
CONTACT:
PD Dr. med. Matthias M. Heck
University Hospital TUM Klinikum rechts der Isar
Department of Urology
Tel: +49 89 4140 2520
matthias.heck@tum.de
Dr. med. Dr. rer. nat. Christof Winter
University Hospital TUM Klinikum rechts der Isar
Institute of Clinical Chemistry and Pathobiochemistry
Tel: +49 89 4140 4765
christof.winter@tum.de
FURTHER INFORMATION:
Department of Urology of TUM
Institute of Clinical Chemistry and Pathobiochemistry of TUM
AR-V7 - CTC's - Risk of Death
