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. VacircaGregory Vidal, Lee Schwartzberg, David D. Halbert, Andreas Voss, Daniel Magee, Mark R. Miglarese, Michael Famulok, Günter Mayer, David Spetzler

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1219
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

breast
cancer
Breast Neoplasms
Ligands
ligands
Area Under Curve
phenotype
Oncology
Molecular interactions
Single-Stranded DNA
Kaplan-Meier Estimate
Testing
molecular interactions
Gene Library
progressions
Tumors
Patient Care
drugs
tumors
deoxyribonucleic acid

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Domenyuk, V., Gatalica, Z., Santhanam, R., Wei, X., Stark, A., Kennedy, P., ... Spetzler, D. (2018). Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes. Nature communications, 9(1), [1219]. https://doi.org/10.1038/s41467-018-03631-z

Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes. / Domenyuk, Valeriy; Gatalica, Zoran; Santhanam, Radhika; Wei, Xixi; Stark, Adam; Kennedy, Patrick; Toussaint, Brandon; Levenberg, Symon; Wang, Jie; Xiao, Nianqing; Greil, Richard; Rinnerthaler, Gabriel; Gampenrieder, Simon P.; Heimberger, Amy B.; Berry, Donald A.; Barker, Anna; Quackenbush, John; Marshall, John L.; Poste, George; Vacirca, Jeffrey L.; Vidal, Gregory; Schwartzberg, Lee; Halbert, David D.; Voss, Andreas; Magee, Daniel; Miglarese, Mark R.; Famulok, Michael; Mayer, Günter; Spetzler, David.

In: Nature communications, Vol. 9, No. 1, 1219, 01.12.2018.

Research output: Contribution to journalArticle

Domenyuk, V, Gatalica, Z, Santhanam, R, Wei, X, Stark, A, Kennedy, P, Toussaint, B, Levenberg, S, Wang, J, Xiao, N, Greil, R, Rinnerthaler, G, Gampenrieder, SP, Heimberger, AB, Berry, DA, Barker, A, Quackenbush, J, Marshall, JL, Poste, G, Vacirca, JL, Vidal, G, Schwartzberg, L, Halbert, DD, Voss, A, Magee, D, Miglarese, MR, Famulok, M, Mayer, G & Spetzler, D 2018, 'Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes', Nature communications, vol. 9, no. 1, 1219. https://doi.org/10.1038/s41467-018-03631-z
Domenyuk, Valeriy ; Gatalica, Zoran ; Santhanam, Radhika ; Wei, Xixi ; Stark, Adam ; Kennedy, Patrick ; Toussaint, Brandon ; Levenberg, Symon ; Wang, Jie ; Xiao, Nianqing ; Greil, Richard ; Rinnerthaler, Gabriel ; Gampenrieder, Simon P. ; Heimberger, Amy B. ; Berry, Donald A. ; Barker, Anna ; Quackenbush, John ; Marshall, John L. ; Poste, George ; Vacirca, Jeffrey L. ; Vidal, Gregory ; Schwartzberg, Lee ; Halbert, David D. ; Voss, Andreas ; Magee, Daniel ; Miglarese, Mark R. ; Famulok, Michael ; Mayer, Günter ; Spetzler, David. / Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes. In: Nature communications. 2018 ; Vol. 9, No. 1.
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