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

AR-V7 Castration-resistant prostate cancer Circulating tumor cells (CTCs) Predictive biomarkers

Journal

Journal of circulating biomarkers
ISSN: 1849-4544
Titre abrégé: J Circ Biomark
Pays: United States
ID NLM: 101703517

Informations de publication

Date de publication:
Historique:
received: 09 06 2020
accepted: 04 09 2020
entrez: 15 3 2021
pubmed: 16 3 2021
medline: 16 3 2021
Statut: epublish

Résumé

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). 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. 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).

Identifiants

pubmed: 33717359
doi: 10.33393/jcb.2020.2163
pmc: PMC7951184
doi:

Types de publication

Journal Article

Langues

eng

Pagination

13-19

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States

Informations de copyright

Copyright © 2020, The Authors.

Déclaration de conflit d'intérêts

Conflict of interest: D. Lu, R. Krupa, M. Harvey, R. Graf, J. Schonhoft, A. Jendrisak, A. Gill, S. Orr are or were employees of Epic Sciences during the writing, data collection, and analysis. H.I. Scher is a consultant/advisory board member for Ambry Genetics Corporation, Amgen, ESSA Pharma, Janssen Biotech, Janssen Research & Development, OncLive Insights, Menarini Silicon Biosystems, Physicians Education Resource, Sanofi Aventis, and WCG Oncology; and he has received institutional research funding from Epic Sciences, Illumina, Janssen Diagnostics, Menarini Silicon Biosystems, and ThermoFisher. No other disclosures are reported.

Références

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Auteurs

David Lu (D)

Epic Sciences, San Diego, California - USA.
Exact Sciences, Madison, Wisconsin - USA.

Rachel Krupa (R)

Epic Sciences, San Diego, California - USA.

Melissa Harvey (M)

Epic Sciences, San Diego, California - USA.

Ryon P Graf (RP)

Epic Sciences, San Diego, California - USA.

Nicole Schreiber (N)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York - USA.
Prostate Cancer Clinical Trials Consortium, New York, New York - USA.

Ethan Barnett (E)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York - USA.

Emily Carbone (E)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York - USA.

Adam Jendrisak (A)

Epic Sciences, San Diego, California - USA.

Audrey Gill (A)

Epic Sciences, San Diego, California - USA.

Sarah Orr (S)

Epic Sciences, San Diego, California - USA.

Howard I Scher (HI)

Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York - USA.
Department of Medicine, Weill Cornell Medical College, New York, New York - USA.

Joseph D Schonhoft (JD)

Epic Sciences, San Diego, California - USA.

Classifications MeSH