Format

Send to

Choose Destination
Neoplasia. 2019 Aug;21(8):802-809. doi: 10.1016/j.neo.2019.06.002. Epub 2019 Jul 2.

Circulating Tumor Cell-Based Molecular Classifier for Predicting Resistance to Abiraterone and Enzalutamide in Metastatic Castration-Resistant Prostate Cancer.

Author information

1
Department of Urology, University of Michigan, Ann Arbor, MI, USA; Department of Urology, Inje University, Haeundae Paik Hospital, Busan, Republic of Korea.
2
Department of Urology, University of Michigan, Ann Arbor, MI, USA; University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
3
Department of Urology, University of Michigan, Ann Arbor, MI, USA; Consulting for Computing, Statistics, and Analytics Research (CSCAR), University of Michigan, Ann Arbor, MI, USA.
4
Department of Urology, University of Michigan, Ann Arbor, MI, USA.
5
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
6
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, Michigan Medicine, Ann Arbor, MI, USA.
7
University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA; Department of Radiation Oncology, Michigan Medicine, Ann Arbor, MI, USA.
8
Department of Hematology/Oncology, University of Michigan, Ann Arbor,MI, USA.
9
Department of Urology, University of Michigan, Ann Arbor, MI, USA; University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA; Department of Urology, Medical University of Vienna, Vienna, Austria.
10
Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
11
Department of Urology, University of Michigan, Ann Arbor, MI, USA; University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
12
Department of Urology, University of Michigan, Ann Arbor, MI, USA; University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA. Electronic address: tomorgan@med.umich.edu.

Abstract

While circulating tumor cell (CTC)-based detection of AR-V7 has been demonstrated to predict patient response to second-generation androgen receptor therapies, the rarity of AR-V7 expression in metastatic castrate-resistant prostate cancer (mCRPC) suggests that other drivers of resistance exist. We sought to use a multiplex gene expression platform to interrogate CTCs and identify potential markers of resistance to abiraterone and enzalutamide. 37 patients with mCRPC initiating treatment with enzalutamide (n = 16) or abiraterone (n = 21) were prospectively enrolled for CTC collection and gene expression analysis using a panel of 89 prostate cancer-related genes. Gene expression from CTCs was correlated with PSA response and radioclinical progression-free survival (PFS) using Kaplan-Meier and Cox regression analyses. Twenty patients (54%) had detectable CTCs. At a median follow-up of 11.3 months, increased expression of the following genes was significantly associated with shorter PSA PFS and radioclinical PFS: AR, AR-V7, PSA, PSCA, TSPAN8, NKX3.1, and WNT5B. Additionally, high SPINK1 expression was associated with increased PFS. A predictive model including all eight genes gave an area under the curve (AUC) of 0.84 for PSA PFS and 0.86 for radioclinical PFS. In comparison, the AR-V7 only model resulted in AUC values of 0.65 and 0.64.These data demonstrate that clinically relevant information regarding gene expression can be obtained from whole blood using a CTC-based approach. Multigene classifiers in this setting may allow for the development of noninvasive predictive biomarkers to guide clinical management.

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center