Development of an immunofluorescent AR-V7 circulating tumor cell assay – A blood-based test for men with metastatic prostate cancer

  • David Lu Epic Sciences, San Diego, California and Exact Sciences, Madison, Wisconsin - USA
  • Rachel Krupa Epic Sciences, San Diego, California - USA
  • Melissa Harvey Epic Sciences, San Diego, California - USA
  • Ryon P. Graf Epic Sciences, San Diego, California - USA
  • Nicole Schreiber Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York and Prostate Cancer Clinical Trials Consortium, New York, New York - USA
  • Ethan Barnette Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York - USA
  • Emily Carbone Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York - USA
  • Adam Jendrisak Epic Sciences, San Diego, California - USA
  • Audrey Gill Epic Sciences, San Diego, California - USA
  • Sarah Orr Epic Sciences, San Diego, California - USA
  • Howard I Scher Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York and Department of Medicine, Weill Cornell Medical College, New York, New York - USA
  • Joseph Daniel Schonhoft Epic Sciences, San Diego, California - USA
Keywords: AR-V7, Castration-resistant prostate cancer, Circulating tumor cells (CTCs), Predictive biomarkers

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 positivity 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).

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Published
2020-10-23
How to Cite
LuD., KrupaR., HarveyM., GrafR., SchreiberN., BarnetteE., CarboneE., JendrisakA., GillA., OrrS., ScherH., & SchonhoftJ. (2020). Development of an immunofluorescent AR-V7 circulating tumor cell assay – A blood-based test for men with metastatic prostate cancer. Journal of Circulating Biomarkers, 9(1), 13-19. https://doi.org/10.33393/jcb.2020.2163
Section
Original research article