Abstract IA20: Molecular and genomic characterization of invasive circulating tumorcells (iCTCs) from men with metastatic castration-resistant prostate cancer (mCRPC)
Authors: Friedlander Terence W. , Premasekharan Gayatri , Dilip Archana , Tawney Jaime , Ngo Vy , Gilbert Elizabeth , Ryan Charles J. , Small Eric , Paris Pamela L. 
Published: May 2015

Background: Molecular characterization and genomic analysis of circulating tumor cells (CTCs) may allow for a better understanding of the mechanisms of resistance to therapies in metastatic castration resistant prostate cancer (mCRPC). The Vitatex VitaAssay platform captures invasive CTCs (iCTCs) in a cell surface marker-independent fashion based on their ability to invade a fluorescently-labeled cell adhesion matrix (CAM), allowing for the analysis of multiple CTC subpopulations. We recently demonstrated our ability to detect EMT and stem-like CTC subpopulations with the CAM platform (Friedlander et al., Int J Cancer 2014). We hypothesize that CTC subpopulation diversity is associated with a shorter period of time to resistance for men with mCRPC. Here we sought to estimate epithelial, mesenchymal, stem-like and neuroendocrine iCTC subpopulation diversity in men with CRPC starting abiraterone acetate or enzalutamide therapy and to report the genomic profiles of iCTCs and matched metastatic biopsies.

Methods: Blood is being obtained with informed consent from men with mCRPC partaking in either a dose escalation abiraterone trial or the West Coast Dream Team (WCDT) trial. iCTCs are being isolated from the blood samples using the CAM platform coupled with FACS. Paired metastatic biopsies are being obtained as part of the WCDT, when available. For CTC enrichment, iCTCs are defined as CAM+/CD45-/CD14-. For subpopulation characterizations, mesenchymal iCTCs are defined as vimentin+, stem-like iCTCs as CD44+ and neuroendocrine iCTCs as chomogranin (CgA)+. Agilent array comparative genomic hybridization (aCGH) of iCTCs and paired biopsies is being performed.

Results: iCTCs were isolated using the CAM platform from 96 men, to date. The average baseline iCTC count per 7.5ml was 160 (range 0-1255). In a subset of 69 subjects, the average baseline CD44+ iCTC count per 7.5ml was 153 (range 0 -1423), and in a subset of 31 patients the median vimentin+ iCTC count per 7.5ml was 116 (range 5-538) and in a subset of 5 patients the median CgA+ iCTC counts per 7.5ml was 79 (range 46 - 185). Using aCGH, copy number aberration is detectable in iCTCs. Some iCTC aCGH profiles resemble paired metastatic biopsy aCGH profiles.

Conclusions: Multiple CRPC iCTC subpopulations are identifiable from men with mCRPC, reflecting the heterogeneity of the disease. Data will continue to be collected as part of these two ongoing clinical trials to identify biomarkers of resistance and shed light on resistance pathways.

Citation Format: Terence W. Friedlander, Gayatri Premasekharan, Archana Dilip, Jaime Tawney, Vy Ngo, Elizabeth Gilbert, Charles J. Ryan, Eric Small, Pamela L. Paris. Molecular and genomic characterization of invasive circulating tumorcells (iCTCs) from men with metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr IA20.