Detection of Androgen Receptor Variant 7 (<i>ARV7)</i> mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer
Expression of the androgen receptor splice variant 7 (<i>ARV7)</i> in circulating tumor cells (CTCs) has been associated with resistance towards novel androgen receptor (AR)-targeting therapies. While a multitude of ARV7 detection approaches have been developed, the simultaneous enumerat...
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| Format: | Article |
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MDPI AG
2019-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/9/1067 |
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| author | Claudia Hille Tobias M. Gorges Sabine Riethdorf Martine Mazel Thomas Steuber Gunhild Von Amsberg Frank König Sven Peine Catherine Alix-Panabières Klaus Pantel |
| author_facet | Claudia Hille Tobias M. Gorges Sabine Riethdorf Martine Mazel Thomas Steuber Gunhild Von Amsberg Frank König Sven Peine Catherine Alix-Panabières Klaus Pantel |
| author_sort | Claudia Hille |
| collection | DOAJ |
| description | Expression of the androgen receptor splice variant 7 (<i>ARV7)</i> in circulating tumor cells (CTCs) has been associated with resistance towards novel androgen receptor (AR)-targeting therapies. While a multitude of ARV7 detection approaches have been developed, the simultaneous enumeration of CTCs and assessment of <i>ARV7</i> status and the integration of validated technologies for CTC enrichment/detection into their workflow render interpretation of the results more difficult and/or require shipment to centralized labs. Here, we describe the establishment and technical validation of a novel <i>ARV7</i> detection method integrating the CellSearch<sup>®</sup> technology, the only FDA-cleared CTC-enrichment method for metastatic prostate cancer available so far. A highly sensitive and specific qPCR-based assay was developed, allowing detection of <i>ARV7</i> and <i>keratin 19</i> transcripts from as low as a single <i>ARV7<sup>+</sup>/K19<sup>+</sup></i> cell, even after 24 h of sample storage. Clinical feasibility was demonstrated on blood samples from 26 prostate cancer patients and assay sensitivity and specificity was corroborated. Our novel approach can now be included into prospective clinical trials aimed to assess the predictive values of CTC/ARV7 measurements in prostate cancer. |
| first_indexed | 2024-03-12T08:06:25Z |
| format | Article |
| id | doaj.art-f91117dbfc2c48d394b161fec833fbd0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:06:25Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f91117dbfc2c48d394b161fec833fbd02023-09-02T19:33:20ZengMDPI AGCells2073-44092019-09-0189106710.3390/cells8091067cells8091067Detection of Androgen Receptor Variant 7 (<i>ARV7)</i> mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate CancerClaudia Hille0Tobias M. Gorges1Sabine Riethdorf2Martine Mazel3Thomas Steuber4Gunhild Von Amsberg5Frank König6Sven Peine7Catherine Alix-Panabières8Klaus Pantel9Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyLaboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier–UM EA2415, 34295 Montpellier, FranceMartini Clinic, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyATURO, Urology Practice, 14197 Berlin, GermanyDepartment of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyLaboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier–UM EA2415, 34295 Montpellier, FranceDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyExpression of the androgen receptor splice variant 7 (<i>ARV7)</i> in circulating tumor cells (CTCs) has been associated with resistance towards novel androgen receptor (AR)-targeting therapies. While a multitude of ARV7 detection approaches have been developed, the simultaneous enumeration of CTCs and assessment of <i>ARV7</i> status and the integration of validated technologies for CTC enrichment/detection into their workflow render interpretation of the results more difficult and/or require shipment to centralized labs. Here, we describe the establishment and technical validation of a novel <i>ARV7</i> detection method integrating the CellSearch<sup>®</sup> technology, the only FDA-cleared CTC-enrichment method for metastatic prostate cancer available so far. A highly sensitive and specific qPCR-based assay was developed, allowing detection of <i>ARV7</i> and <i>keratin 19</i> transcripts from as low as a single <i>ARV7<sup>+</sup>/K19<sup>+</sup></i> cell, even after 24 h of sample storage. Clinical feasibility was demonstrated on blood samples from 26 prostate cancer patients and assay sensitivity and specificity was corroborated. Our novel approach can now be included into prospective clinical trials aimed to assess the predictive values of CTC/ARV7 measurements in prostate cancer.https://www.mdpi.com/2073-4409/8/9/1067prostate cancerbiomarkerscirculating tumor cellsandrogen receptorARV7abirateroneenzalutamide |
| spellingShingle | Claudia Hille Tobias M. Gorges Sabine Riethdorf Martine Mazel Thomas Steuber Gunhild Von Amsberg Frank König Sven Peine Catherine Alix-Panabières Klaus Pantel Detection of Androgen Receptor Variant 7 (<i>ARV7)</i> mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer Cells prostate cancer biomarkers circulating tumor cells androgen receptor ARV7 abiraterone enzalutamide |
| title | Detection of Androgen Receptor Variant 7 (<i>ARV7)</i> mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer |
| title_full | Detection of Androgen Receptor Variant 7 (<i>ARV7)</i> mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer |
| title_fullStr | Detection of Androgen Receptor Variant 7 (<i>ARV7)</i> mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer |
| title_full_unstemmed | Detection of Androgen Receptor Variant 7 (<i>ARV7)</i> mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer |
| title_short | Detection of Androgen Receptor Variant 7 (<i>ARV7)</i> mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer |
| title_sort | detection of androgen receptor variant 7 i arv7 i mrna levels in epcam enriched ctc fractions for monitoring response to androgen targeting therapies in prostate cancer |
| topic | prostate cancer biomarkers circulating tumor cells androgen receptor ARV7 abiraterone enzalutamide |
| url | https://www.mdpi.com/2073-4409/8/9/1067 |
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