The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients: Beyond the Abstract

Several studies have been published about a possible role of AR-V7 detection in CTCs as a biomarker of resistance to novel hormonal agents in CRPC patients. However, AR-V7 detection in CTCs can be troublesome because of several issues: it requires specific instrumentations and the cost of the procedure is substantial [1, 2].

Moreover, one of the major issues regarding CTC isolation is their heterogeneity; in particular, there is a wide morphologic, immunologic and phenotypic variation within CTCs obtained from the same patient. In addition, due to the epithelial-to-mesenchymal transition processes, the expression of the epithelial markers on CTC surface may be down-regulated, making their detection less efficient [3, 4]. 

We then decided to explore a new methodology that can be routinely appliable in clinical practice and reproducible. The comparison of CTCs vs plasma-derived exosomes as a source of RNA demonstrates that the analysis of RNA from exosomes could be more sensitive and accurate than CTCs. Indeed, by analysing the PFS obtained from our study [5] and the one observed in the published trial on CTCs [6], we found that, by analysing exosome-derived RNA, AR-V7-negative patients have a higher PFS compared to AR-V7-negative patients in CTCs. This could be related to false negative samples in the cohort of patients whose RNA was extracted from CTCs, because these patients may have mutations detectable in exosomes but undetected in CTCs, thus reflecting a higher sensitivity of the exosome approach over CTCs.

This study was made on a small number of patients, but it is powered to demonstrate a possible role for AR-V7 detection on exosomes-derived RNA in current diagnostic approach. However, further studies on a larger number of patients and prospective clinical trials are needed to confirm such role. 

Written by:

Marzia Del Re, Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy

Elisa Biasco, Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Italy


Andrea Sbrana, Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Italy


Luca Galli, Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Italy


Romano Danesi, Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy


References:

1. Gold B, Cankovic M, Furtado LV, Meier F, Gocke CD. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility?. A report of the association for molecular pathology. J Mol Diagn 2015;17:209–24.

2. Wicha MS, Hayes DF. Circulating tumor cells: not all detected cells are bad and not all bad cells are detected. J Clin Oncol 2011;29: 1508–11.

3. Bin Hong, Youli Zu. Detecting Circulating Tumor Cells: Current Challenges and New Trends. Theranostics. 2013; 3(6): 377–394

4. Wicha MS, Hayes DF. Circulating tumor cells: not all detected cells are bad and not all bad cells are detected. J Clin Oncol. 2011;29(12):1508–1511

5. Del Re M, Biasco E, Crucitta S, et al. The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients. Eur Urol. 2016 Aug 26. doi: 10.1016/j.eururo.2016.08.012

6. Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014;371(11):1028-38


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