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Cancer Discov. 2018 Mar;8(3):288-303. doi: 10.1158/2159-8290.CD-16-1406. Epub 2018 Jan 4.

An RNA-Based Digital Circulating Tumor Cell Signature Is Predictive of Drug Response and Early Dissemination in Prostate Cancer.

Author information

1
Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
2
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
3
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
4
Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
5
Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
6
Department of Pathology, Harvard Medical School, Boston, Massachusetts.
7
Center for Engineering in Medicine, Massachusetts General Hospital, Boston, Massachusetts.
8
Department of Surgery, Harvard Medical School, Boston, Massachusetts.
9
Massachusetts General Hospital Cancer Center, Boston, Massachusetts. dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu.
10
Howard Hughes Medical Institute, Chevy Chase, Maryland.
#
Contributed equally

Abstract

Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTC) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 patients with metastatic castration-resistant prostate cancer treated with first-line abiraterone, pretreatment elevation of the digital CTCM score identifies a high-risk population with poor overall survival (HR = 6.0; P = 0.01) and short radiographic progression-free survival (HR = 3.2; P = 0.046). Expression of HOXB13 in CTCs identifies 6 of 6 patients with ≤12-month survival, with a subset also expressing the ARV7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTCL score predicts microscopic dissemination to seminal vesicles and/or lymph nodes (P < 0.001). Thus, digital quantitation of CTC-specific transcripts enables noninvasive monitoring that may guide treatment selection in both metastatic and localized prostate cancer.Significance: There is an unmet need for biomarkers to guide prostate cancer therapies, for curative treatment of localized cancer and for application of molecularly targeted agents in metastatic disease. Digital quantitation of prostate CTC-derived transcripts in blood specimens is predictive of abiraterone response in metastatic cancer and of early dissemination in localized cancer. Cancer Discov; 8(3); 288-303. ©2018 AACR.See related commentary by Heitzer and Speicher, p. 269This article is highlighted in the In This Issue feature, p. 253.

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