Genetic variants and enzyme activity in citidin deaminase: Relationship with capecitabine toxicity and recommendation for dose adjustment
Objective: Capecitabine, an antineoplastic drug used in the treatment of breast and colon cancer, can cause se-vere, even fatal toxicity in some patients. The interindividual variability of this toxicity is largely due to genetic variations in target genes and enzymes of metabolism of this drug, suc...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| Repositorio: | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| OAI Identifier: | oai:isabial.fundanetsuite.com:p10030 |
| Acceso en línea: | https://isabial.portalinvestigacion.com/publicaciones10030 |
| Access Level: | acceso abierto |
| Palabra clave: | Capecitabine Citidin deaminase Pharmacogenetics Precision medicine Clinical protocols Toxicity |
| Sumario: | Objective: Capecitabine, an antineoplastic drug used in the treatment of breast and colon cancer, can cause se-vere, even fatal toxicity in some patients. The interindividual variability of this toxicity is largely due to genetic variations in target genes and enzymes of metabolism of this drug, such as thymidylate synthase and dihydropyrimidine dehydrogenase. The enzyme cytidine deaminase (CDA), involved in the activation of capeci-tabine, also has several variants associated with an increased risk of toxicity to treatment, although its role as a biomarker is not yet clearly defined.Therefore, our main objective is to study the association between the presence of genetic variants in CDA gen, CDA enzymatic activity and the development of severe toxicity in patients treated with capecitabine whose initial dose was adjusted based on the genetic profile of the dihydropyrimidine dehydrogenase gen (DPYD). Method: Prospective multicenter observational cohort study, focused on the analysis of the genotype-phenotype association of the CDA enzyme.After the experimental phase, an algorithm will be developed to determine the dose adjustment needed to re-duce the risk of treatment toxicity according to CDA genotype, developing a clinical guide for capecitabine dosing according to genetic variants in DPYD and CDA. Based on this guide, a Bioinformatics Tool will be created to gen-erate the pharmacotherapeutic report automatically, facilitating the implementation of pharmacogenetic advice in clinical practice. This tool will be a great support in making pharmacotherapeutic decisions based on the patient's genetic profile, incorporating precision medicine into clinical routine. Once the usefulness of this tool has been validated, it will be offered free of charge to facilitate the implementation of pharmacogenetics in hos-pital centers and equitably benefit all patients on capecitabine treatment.& COPY; 2022 The Authors. Published by Elsevier Espana, S.E.F.H. This is an open access article under the license CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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