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

Abstract

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.

Effect of Estrogen Receptor Status on Circulatory Immune and Metabolomics Profiles of HER2-Positive Breast Cancer Patients Enrolled for Neoadjuvant Targeted Chemotherapy

“…Thus, metabolomics not only can potentially identify the biochemical signals directly caused by the presence of cancer, but it can also detect the interaction between cancer and host, which is mainly mediated by the immune system. In the BC field, the potential of metabolomics in blood serum or plasma has been explored to identify new biomarkers useful for early diagnosis and prognosis [14][15][16][17][18][19][20][21][22][23][24].…”

Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis

“…Cancer cells are highly metabolically active, which is both cause and consequence of their pathogenesis, but this may also represent an opportunity for diagnosis and treatment. The analysis of the metabolome in body fluids is emerging as a diagnostic strategy that could be associated with the progression of the disease . In this context, the aim of the present study was to determine serum metabolomic profiles in the search of accurate diagnostic biomarkers that could be used to distinguish iCCA from HCC or PSC, and also for the early diagnosis of these diseases.…”

Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine

“…Early studies in humans led by the pharmacometabolomics network illustrated the promise of using metabolic profiles both at baseline and during treatment to define mechanism of action and mechanism of variation of response to treatment in ten classes of therapies. To date, PMx has been applied to study many drug classes, including antipsychotics [14,68], statins [69,70], antidepressants [19], antiplatelets [39], antihypertensives [21,71,72], cancer therapies [73,74], aspirin [75,76], metformin [72], and drug therapy side effect of treatment for amyotrophic lateral sclerosis (ALS) [77]. Novel insights were derived for each drug, illustrating that in most cases numerous biochemical pathways are impacted in a correlated way.…”