Evidence map›Paper›PMID 27401243›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2017

Integrated Analysis of Multiple Biomarkers from Circulating Tumor Cells Enabled by Exclusion-Based Analyte Isolation.

Jamie M Sperger, Lindsay N Strotman, Allison Welsh, Benjamin P Casavant, Zachery Chalmers, Sacha Horn, Erika Heninger, Stephanie M Thiede, Jacob Tokar, Benjamin K Gibbs and 7 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed.

  1. Phase II Multicenter Study of Enzalutamide in Metastatic Castration-Resistant Prostate Cancer to Identify Mechanisms Driving Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
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  14. Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  15. Review
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  17. Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Jamie M SpergerDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
Lindsay N StrotmanDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
Allison WelshFoundation Medicine, Cambridge, Massachusetts.
Benjamin P CasavantDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
Zachery ChalmersFoundation Medicine, Cambridge, Massachusetts.
Sacha HornCarbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
Erika HeningerCarbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
Stephanie M ThiedeCarbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
Jacob TokarDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
Benjamin K GibbsCarbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
David J GuckenbergerDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
Lakeesha CarmichaelDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin.
Scott M DehmMasonic Cancer Center and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
Philip J StephensFoundation Medicine, Cambridge, Massachusetts.
David J BeebeDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
Scott M BerryDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
Joshua M LangDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin. jmlang@medicine.wisc.edu.

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
AR Gene Rearrangements and AR Signaling in Prostate CancerR01CA174777 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2013 to 2026
$4.9M
VERSA: An Integrated, Multi-Endpoint Platform for Circulating Tumor Cell AnalysisR01CA181648 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI BERRY, SCOTT M, LANG, JOSHUA MICHAEL · 2014 to 2018
$1.6M
Microchannel cell-based assays to enable cancer researchR33CA137673 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI BEEBE, DAVID J · 2009 to 2011
$1.4M
NCATS NIH HHS UL1 TR000114NCI NIH HHS R01 CA174777NCI NIH HHS R01 CA181648NCI NIH HHS R33 CA137673
6 · The paper itself

Abstract

purposeThere is a critical clinical need for new predictive and pharmacodynamic biomarkers that evaluate pathway activity in patients treated with targeted therapies. A microscale platform known as VERSA (versatile exclusion-based rare sample analysis) was developed to integrate readouts across protein, mRNA, and DNA in circulating tumor cells (CTC) for a comprehensive analysis of the androgen receptor (AR) signaling pathway. EXPERIMENTAL

designUtilizing exclusion-based sample preparation principles, a handheld chip was developed to perform CTC capture, enumeration, quantification, and subcellular localization of proteins and extraction of mRNA and DNA. This technology was validated across integrated endpoints in cell lines and a cohort of patients with castrate-resistant prostate cancer (CRPC) treated with AR-targeted therapies and chemotherapies.

resultsThe VERSA was validated in cell lines to analyze AR protein expression, nuclear localization, and gene expression targets. When applied to a cohort of patients, radiographic progression was predicted by the presence of multiple AR splice variants and activity in the canonical AR signaling pathway. AR protein expression and nuclear localization identified phenotypic heterogeneity. Next-generation sequencing with the FoundationOne panel detected copy number changes and point mutations. Longitudinal analysis of CTCs identified acquisition of multiple AR variants during targeted treatments and chemotherapy.

conclusionsComplex mechanisms of resistance to AR-targeted therapies, across RNA, DNA, and protein endpoints, exist in patients with CRPC and can be quantified in CTCs. Interrogation of the AR signaling pathway revealed distinct patterns relevant to tumor progression and can serve as pharmacodynamic biomarkers for targeted therapies. Clin Cancer Res; 1-11. ©2016 AACR.

Identifiers

PMID27401243
PMCPMC5226928

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.