Mass Spectrometry‐based Personalized Drug Therapy

Abstract

Personalized drug therapy aims to provide tailored treatment for individual patient. Mass spectrometry (MS) is revolutionarily involved in this area because MS is a rapid, customizable, cost‐effective, and easy to be used high‐throughput method with high sensitivity, specificity, and accuracy. It is driving the formation of a new field, MS‐based personalized drug therapy, which currently mainly includes five subfields: therapeutic drug monitoring (TDM), pharmacogenomics (PGx), pharmacomicrobiomics, pharmacoepigenomics, and immunopeptidomics. Gas chromatography‐MS (GC‐MS) and liquid chromatography‐MS (LC‐MS) are considered as the gold standard for TDM, which can be used to optimize drug dosage. Matrix‐assisted laser desorption ionization‐time of flight‐MS (MALDI‐TOF‐MS) significantly improves the capability of detecting biomacromolecule, and largely promotes the application of MS in PGx. It is becoming an indispensable tool for genotyping, which is used to discover and validate genetic biomarkers. In addition, MALDI‐TOF‐MS also plays important roles in identity of human microbiome whose diversity can explain interindividual differences of drug response. Pharmacoepigenetics is to study the role of epigenetic factors in individualized drug treatment. MS can be used to discover and validate pharmacoepigenetic markers (DNA methylation, histone modification, and noncoding RNA). For the emerging cancer immunotherapy, personalized cancer vaccine has effective immunotherapeutic activity in the clinic. MS‐based immunopeptidomics can effectively discover and screen neoantigens. This article systematically reviewed MS‐based personalized drug therapy in the above mentioned five subfields. © 2020 John Wiley & Sons Ltd. Mass Spec Rev

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age

“…Mass spectrometer generates multiple ions from the sample and separates these ions according to their specific mass-to-charge ratio, recording relative abundance of each ion type [56]. LC-MS/MS represents now the gold standard for TDM [25] and offers many advantages in its application in neonatal TDM: sensitivity, precision and accuracy, even with small amounts of samples, as the technique is very sensitive with small concentrations of analytes [2,25]. The benefits of MS are speed of analysis, simple preparation of samples and multiple analytes' determination in one short run [54].…”

“…Even if patients receive the same drug doses, a different response could be obtained: the first objective of the Therapeutic Drug Monitoring (TDM) is to measure plasma drug concentrations to adjust and personalize the drug dosage and administration [25]. Not all drugs require TDM.…”

NMD inhibition by 5-azacytidine augments presentation of immunogenic frameshift-derived neoepitopes

“…Neoepitopes are commonly identified by evaluating in silico candidates using T cell screening technologies. However, such analyses are strongly limited by high rates of false-positive results (Andreatta and Nielsen, 2016;Bassani-Sternberg et al, 2015;Cui et al, 2020;Freudenmann et al, 2018). Recent breakthroughs in the sensitivity and reproducibility of mass spectrometry (MS) help to overcome these disadvantages and enable the unbiased exploration of the global immunopeptidome presented by the HLA system.…”

Application of Mass Spectrometry in Pancreatic Cancer Translational Research

“…Specifically, MALDI-TOF MS is capable of directly determining unseparated macromolecular mixtures. It should be noted that MALDI-TOF MS cannot effectively identify small molecular peptides with a relative molecular weight of less than 500 ( 22 ). Unlike MALDI-TOF-MS in the detection of biological macromolecules, laser ablation-plasma MS (LA-ICP MS) is more widely used to determine the elemental composition of natural and synthetic materials.…”