Pharmacometabolomics of trabectedin in metastatic soft tissue sarcoma patients

Corona, Giuseppe; Di Gregorio, Emanuela; Buonadonna, Angela; Lombardi, Davide; Scalone, Simona; Steffan, Agostino; Miolo, Gianmaria

doi:10.3389/fphar.2023.1212634

Cited by 4 publications

(2 citation statements)

References 53 publications

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“…Moreover, its response matrix has a prediction function, which is an advantageous method that meets the requirements of pharmacometabolomics data analysis. In addition, the correlation analysis of pharmacokinetic and metabolomics data will also use conventional analysis methods for calculating correlation coefficients, such as Pearman correlation coefficient and Spearman correlation coefficient [65,66,153]. Furthermore, the participation of machine learning methods in modeling also enhances the precision and efficiency of data analysis within the realm of pharmacometabolomics.…”

Section: Pharmacometabolomics Informs Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics in Pharmacometabolomics: Towards Personalized Medication

Jian,

He,

Gao

et al. 2023

Pharmaceuticals

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Indiscriminate drug administration may lead to drug therapy results with varying effects on patients, and the proposal of personalized medication can help patients to receive effective drug therapy. Conventional ways of personalized medication, such as pharmacogenomics and therapeutic drug monitoring (TDM), can only be implemented from a single perspective. The development of pharmacometabolomics provides a research method for the realization of precise drug administration, which integrates the environmental and genetic factors, and applies metabolomics technology to study how to predict different drug therapeutic responses of organisms based on baseline metabolic levels. The published research on pharmacometabolomics has achieved satisfactory results in predicting the pharmacokinetics, pharmacodynamics, and the discovery of biomarkers of drugs. Among them, the pharmacokinetics related to pharmacometabolomics are used to explore individual variability in drug metabolism from the level of metabolism of the drugs in vivo and the level of endogenous metabolite changes. By searching for relevant literature with the keyword “pharmacometabolomics” on the two major literature retrieval websites, PubMed and Web of Science, from 2006 to 2023, we reviewed articles in the field of pharmacometabolomics that incorporated pharmacokinetics into their research. This review explains the therapeutic effects of drugs on the body from the perspective of endogenous metabolites and pharmacokinetic principles, and reports the latest advances in pharmacometabolomics related to pharmacokinetics to provide research ideas and methods for advancing the implementation of personalized medication.

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Section: Pharmacometabolomics Informs Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics in Pharmacometabolomics: Towards Personalized Medication

Jian,

He,

Gao

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

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“…Variability in treatment response and tolerability can also be influenced by individual differences of drug clearance rates. We recently reported an unexpected distinct inverse relationship between drug clearance rates and treatment response of mSTS [15]. Taking into account a group of mSTS patients, the present investigation focused on a 54-year-old patient with LMS who received an extraordinary clinical benefit from the trabectedin treatment that spanned over 73 cycles.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Clues to Bile Acid Patterns and Prolonged Survival in Patients with Metastatic Soft-Tissue Sarcoma Treated with Trabectedin

Miolo,

Buonadonna,

Scalone

et al. 2023

Metabolites

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Metastatic soft-tissue sarcomas (mSTS) encompass a highly heterogeneous group of rare tumours characterized by different clinical behaviours and outcomes. Currently, prognostic factors for mSTS are very limited, posing significant challenges in predicting patient survival. Within a cohort of 39 mSTS patients undergoing trabectedin treatment, it was remarkable to find one patient who underwent 73 cycles of trabectedin achieving an unforeseen clinical outcome. To identify contributing factors to her exceptional long-term survival, we have explored circulation metabolomics and biohumoral biomarkers to uncover a potential distinct host biochemical phenotype. The long-term survival patient compared with the other mSTS patients exhibited a distinctive metabolic profile characterized by remarkably higher levels of ursodeoxycholic acid (UDCA) derivatives and vitamin D and lower levels of lithocholic acid (LCA) derivatives, as well as reduced levels of inflammatory C-Reactive Protein 4 (C-RP4) biomarker. Despite its exploratory nature, this study reveals a potential association between specific bile acid metabolic profiles and mSTS patients’ prognosis. Enhanced clinical understanding of the interplay between bile acid metabolism and disease progression could pave the way for new targeted therapeutic interventions which may improve the overall survival of mSTS patients.

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