Development of an immunofluorescent AR-V7 circulating tumor cell assay - A blood-based test for men with metastatic prostate cancer Journal Article
| Authors: | Lu, D.; Krupa, R.; Harvey, M.; Graf, R. P.; Schreiber, N.; Barnett, E.; Carbone, E.; Jendrisak, A.; Gill, A.; Orr, S.; Scher, H. I.; Schonhoft, J. D. |
| Article Title: | Development of an immunofluorescent AR-V7 circulating tumor cell assay - A blood-based test for men with metastatic prostate cancer |
| Abstract: | Introduction: Here we describe the development of a protein immunofluorescent assay for the detection of nuclear-localized androgen receptor variant 7 (AR-V7) protein within circulating tumor cells (CTCs) identified in patient blood samples. Used in the clinic, the test result serves as a validated biomarker of futility for patients with progressing metastatic castration-resistant prostate cancer (mCRPC) who are treated with androgen receptor targeted therapies (AATT) in whom nuclear-localized AR-V7 CTCs are identified and have received level 2A evidence in the 2019 National Cancer Center Network (NCCN) guidelines (v1.0). Methods: Assay development was completed on the Epic Sciences rare cell detection platform using control cell lines of known AR-V7 status and clinical testing of mCRPC patient samples obtained at the decision point in management. Results and conclusions: Using these samples, all assay parameters, scoring criteria, and clinical cutoffs for posi-tivity were prospectively selected and locked. After assay lock, blinded clinical validation testing was initiated on multiple, independent, clinical cohorts as reported by Scher et al (JAMA Oncol. 2016;2:1441-1449; JAMA Oncol. 2018;4:1179-1186) and Armstrong et al (J Clin Oncol. 2019;37:1120-1129). © 2020 The Authors. |
| Keywords: | controlled study; human tissue; protein expression; unclassified drug; human cell; biological marker; quality control; gene expression; practice guideline; cell assay; genetic transfection; messenger rna; blood sampling; western blotting; androgen receptor; real time polymerase chain reaction; rna extraction; circulating tumor cell; molecularly targeted therapy; castration-resistant prostate cancer; predictive biomarkers; human; male; article; metastatic castration resistant prostate cancer; confocal laser scanning microscopy; immunofluorescence assay; circulating tumor cells (ctcs); 4',6 diamidino 2 phenylindole; ar-v7; androgen receptor variant 7 |
| Journal Title: | Journal of Circulating Biomarkers |
| Volume: | 9 |
| Issue: | 1 |
| ISSN: | 1849-4544 |
| Publisher: | Sage Publications Ltd. |
| Date Published: | 2020-01-01 |
| Start Page: | 13 |
| End Page: | 19 |
| Language: | English |
| DOI: | 10.33393/jcb.2020.2163 |
| PROVIDER: | scopus |
| PMCID: | PMC7951184 |
| PUBMED: | 33717359 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
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