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

Valeriy Domenyuk, Zoran Gatalica, Radhika Santhanam, Xixi Wei, Adam Stark, Patrick Kennedy, Brandon Toussaint, Symon Levenberg, Jie Wang, Nianqing Xiao, Richard Greil, Gabriel Rinnerthaler, Simon P. Gampenrieder, Amy B. Heimberger, Donald A. Berry, Anna Barker, John Quackenbush, John L. Marshall, George Poste, Jeffrey L. Vacirca, Gregory A. Vidal, Lee S. Schwartzberg, David D. Halbert, Andreas Voss, Daniel Magee, Mark R. Miglarese, Michael Famulok (), Günter Mayer () and David Spetzler ()
Additional contact information
Valeriy Domenyuk: Caris Life Sciences
Zoran Gatalica: Caris Life Sciences
Radhika Santhanam: Caris Life Sciences
Xixi Wei: Caris Life Sciences
Adam Stark: Caris Life Sciences
Patrick Kennedy: Caris Life Sciences
Brandon Toussaint: Caris Life Sciences
Symon Levenberg: Caris Life Sciences
Jie Wang: Caris Life Sciences
Nianqing Xiao: Caris Life Sciences
Richard Greil: Paracelsus Medical University Salzburg, Austria and Salzburg Cancer Research Institute, and Cancer Cluster Salzburg
Gabriel Rinnerthaler: Paracelsus Medical University Salzburg, Austria and Salzburg Cancer Research Institute, and Cancer Cluster Salzburg
Simon P. Gampenrieder: Paracelsus Medical University Salzburg, Austria and Salzburg Cancer Research Institute, and Cancer Cluster Salzburg
Amy B. Heimberger: University of Texas MD Anderson Cancer Center
Donald A. Berry: Berry Consultants
Anna Barker: Arizona State University
John Quackenbush: Dana-Farber Cancer Institute
John L. Marshall: Georgetown University Medical Center
George Poste: Caris Life Sciences
Jeffrey L. Vacirca: North Shore Hematology Oncology Associates Cancer Center
Gregory A. Vidal: University of Tennessee Health Science Center
Lee S. Schwartzberg: University of Tennessee Health Science Center
David D. Halbert: Caris Life Sciences
Andreas Voss: Caris Life Sciences
Daniel Magee: Caris Life Sciences
Mark R. Miglarese: Caris Life Sciences
Michael Famulok: Caris Life Sciences
Günter Mayer: Caris Life Sciences
David Spetzler: Caris Life Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03631-z

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