Phenotypic heterogeneity of circulating tumor cells informs clinical decisions between AR signaling inhibitors and taxanes in metastatic prostate cancer Journal Article


Authors: Scher, H. I.; Graf, R. P.; Schreiber, N. A.; McLaughlin, B.; Jendrisak, A.; Wang, Y.; Lee, J.; Greene, S.; Krupa, R.; Lu, D.; Bamford, P.; Louw, J. E.; Dugan, L.; Vargas, H. A.; Fleisher, M.; Landers, M.; Heller, G.; Dittamore, R.
Article Title: Phenotypic heterogeneity of circulating tumor cells informs clinical decisions between AR signaling inhibitors and taxanes in metastatic prostate cancer
Abstract: The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a College of American Pathologists–accredited and Clinical Laboratory Improvement Amendments–certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTC) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified on the basis of the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of the second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients. ©2017 AACR.
Journal Title: Cancer Research
Volume: 77
Issue: 20
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2017-10-15
Start Page: 5687
End Page: 5698
Language: English
DOI: 10.1158/0008-5472.can-17-1353
PROVIDER: scopus
PMCID: PMC5666339
PUBMED: 28819021
DOI/URL:
Notes: Article -- Export Date: 2 November 2017 -- Source: Scopus
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MSK Authors
  1. Glenn Heller
    295 Heller
  2. Martin Fleisher
    237 Fleisher
  3. Howard Scher
    817 Scher