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Nat Commun. 2018 Mar 23;9(1):1219. doi: 10.1038/s41467-018-03631-z.

Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes.

Author information

1
Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.
2
IIIrd Medical Department, Oncologic Center, Paracelsus Medical University Salzburg, Austria and Salzburg Cancer Research Institute, and Cancer Cluster Salzburg, Müllner Hauptstraße, 48A-5020, Salzburg, Austria.
3
Department of Neurosurgery, University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX, 77030, USA.
4
Berry Consultants, LLC, 3345 Bee Caves Road, Suite 201, Austin, TX, 78746, USA.
5
Complex Adaptive Systems Initiative, Arizona State University, 1475N. Scottsdale Road, Suite 361, Scottsdale, AZ, 85257, USA.
6
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215-5450, USA.
7
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Reservoir Road, N.W., Washington, DC, 20057, USA.
8
North Shore Hematology Oncology Associates Cancer Center, 226N Belle Mead Road, East Setauket, NY, 11733, USA.
9
Division of Hematology and Oncology, University of Tennessee Health Science Center, 7945 Wolf River Boulevard, Memphis, TN, 38138, USA.
10
Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA. m.famulok@uni-bonn.de.
11
LIMES Program Unit Chemical Biology & Medicinal Chemistry, c/o Kekulé Institute for Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany. m.famulok@uni-bonn.de.
12
Chemical Biology Max-Planck-Fellowship Group, Center of Advanced European Studies and Research (CAESAR), Ludwig-Erhard-Allee 2, 53175, Bonn, Germany. m.famulok@uni-bonn.de.
13
Center of Aptamer Research and Development, University of Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany. m.famulok@uni-bonn.de.
14
Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA. gmayer@uni-bonn.de.
15
LIMES Program Unit Chemical Biology & Medicinal Chemistry, c/o Kekulé Institute for Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany. gmayer@uni-bonn.de.
16
Center of Aptamer Research and Development, University of Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany. gmayer@uni-bonn.de.
17
Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA. dspetzler@carisls.com.

Abstract

Assessing the phenotypic diversity underlying tumour progression requires the identification of variations in the respective molecular interaction networks. Here we report proof-of-concept for a platform called poly-ligand profiling (PLP) that surveys these system states and distinguishes breast cancer patients who did or did not derive benefit from trastuzumab. We perform tissue-SELEX on breast cancer specimens to enrich single-stranded DNA (ssDNA) libraries that preferentially interact with molecular components associated with the two clinical phenotypes. Testing of independent sample sets verifies the ability of PLP to classify trastuzumab-treated patients according to their clinical outcomes with ROC-AUC of 0.78. Standard HER2 testing of the same patients gives a ROC-AUC of 0.47. Kaplan-Meier analysis reveals a median increase in benefit from trastuzumab-containing treatments of 300 days for PLP-positive compared to PLP-negative patients. If prospectively validated, PLP may increase success rates in precision oncology and clinical trials, thus improving both patient care and drug development.

PMID:
29572535
PMCID:
PMC5865185
DOI:
10.1038/s41467-018-03631-z
[Indexed for MEDLINE]
Free PMC Article

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