Research Papers:

Pharmacometabolomics study identifies circulating spermidine and tryptophan as potential biomarkers associated with the complete pathological response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer

Gianmaria Miolo, Elena Muraro, Donatella Caruso, Diana Crivellari, Anthony Ash, Simona Scalone, Davide Lombardi, Flavio Rizzolio, Antonio Giordano and Giuseppe Corona _

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Oncotarget. 2016; 7:39809-39822. https://doi.org/10.18632/oncotarget.9489

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Gianmaria Miolo1, Elena Muraro2, Donatella Caruso3, Diana Crivellari1, Anthony Ash4, Simona Scalone1, Davide Lombardi1, Flavio Rizzolio2, Antonio Giordano5, Giuseppe Corona2

1Department of Medical Oncology, IRCCS-National Cancer Institute, Aviano, Italy

2Department of Translational Research, IRCCS-National Cancer Institute, Aviano, Italy

3Department of Pharmacological and Bimolecular Science, University of Milan, Milan, Italy

4Department of Biological Chemistry, Norwich Research Park, Norwich, United Kingdom

5Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA

Correspondence to:

Giuseppe Corona, email: [email protected]

Keywords: pharmacometabolomics, pharmacometabonomics, metabolomics, breast, cancer

Received: October 30, 2015     Accepted: April 28, 2016     Published: May 19, 2016


Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. In the present study, we applied a pharmacometabolomics approach to identify biomarkers potentially associated with pathological complete response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer patients. Based on histological response the 34 patients enrolled in the study were subdivided into two groups: good responders (n = 15) and poor responders (n = 19). The pre-treatment serum targeted metabolomics profile of all patients were analyzed by liquid chromatography tandem mass spectrometry and the differences in the metabolomics profile between the two groups was investigated by multivariate partial least squares discrimination analysis. The most relevant metabolites that differentiate the two groups of patients were spermidine and tryptophan. The Good responders showed higher levels of spermidine and lower amounts of tryptophan compared with the poor responders (p < 0.001, q < 0.05). The serum level of these two metabolites identified patients who achieved a pathological complete response with a sensitivity of 90% [0.79–1.00] and a specificity of 0.87% [0.67–1.00]. These preliminary results support the role played by the individual patients’ metabolism in determining the response to cancer treatments and may be a useful tool to select patients that are more likely to benefit from the trastuzumab-paclitaxel treatment.

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