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Journal Article

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

MPS-Authors

Famulok,  Michael
Max Planck Fellow Chemical Biology, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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s41467-018-03631-z.pdf
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Citation

Domenyuk, V., Gatalica, Z., Santhanam, R., Wei, X., Stark, A., Kennedy, P., et al. (2018). Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes. Nature Communications, 9: 1219. doi:10.1038/s41467-018-03631-z.


Cite as: http://hdl.handle.net/21.11116/0000-0003-4AF5-6
Abstract
Assessing the phenotypic diversity underlying tumour progression requires the identification of variations in the respective molecular interaction networks. Here we report proof-ofconcept 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.