Androgen receptor amplification is concordant between circulating tumor cells and biopsies from men undergoing treatment for metastatic castration resistant prostate cancer.

Jennifer Podolak,Jack Youngren,Eric J Small,Erin Tucker,Julie N Graff,Rachel Slottke,Timothy Newby,Tomasz M Beer,Hui-Wen Lue,George V Thomas,Rahul Aggarwal,Susan B Olson,Joshi J Alumkal,Kristi Eilers

doi:10.18632/oncotarget.16169

Jennifer Podolak, Jack Youngren + Show 12 more

Open Access

https://doi.org/10.18632/oncotarget.16169

Copy DOI

Abstract

Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH). AR gene status in CTCs showed strong concordance with AR gene status in matched tissue samples in 24 of 25 patients (Correlation: 96%; Kappa: 0.83; Sensitivity: 100%, Specificity: 83%). Our work demonstrates that AR amplification is conserved between CTCs and biopsies and that CTCs can serve as non-invasive surrogate to document AR amplification in mCRPC.

Highlights

androgen receptor (AR) signaling is the primary driver of prostate cancer, and subsequently, medical castration with androgen deprivation therapy (ADT) is the backbone of all treatments in men with metastatic prostate cancer [1,2,3,4]
Hematogenous dissemination of cancer cells is a critical step in the development of metastases
Hematogenous dissemination of cancer cells is a critical step in the development of metastases [12]

Summary

Introduction

AR signaling is the primary driver of prostate cancer, and subsequently, medical castration with androgen deprivation therapy (ADT) is the backbone of all treatments in men with metastatic prostate cancer [1,2,3,4]. These tumors invariably become resistant to ADT, with the emergence of CRPC, which is fatal. The majority of spatially distinct metastases within individual patients with mCRPC continue to exhibit increased AR signaling [5]. We developed a platformagnostic protocol to capture CTCs and to measure AR amplification status in CTCs from men with mCRPC undergoing treatment, and we evaluated the concordance of AR amplification status with matched metastatic biopsies

Objectives

Methods

Results

Conclusion