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DOI: 10.5935/2526-8732.20210003
Pharmacogenomic tests in Oncology - finding the right dose
Testes farmacogenômicos em oncologia: encontrando a dose certa
Financial support: none to declare.ABSTRACT
A pharmacogenetics/genomics (PGx) anticancer drug testing program is being developed by Kurtz and his group at the Brazilian National Cancer Institute (INCA). Drug -gene pairs were selected for PGx testing based on the presence of clinically validated PGx associations and the availability of international guidelines with PGx-informed dosing recommendations. Fluoropyrimidines-DPYD, irinotecan-UGT1A1 and thiopurines-TPMT/NUDT15 were initially included. The current estimation of anticancer therapy doses usually does not reflect the complexities of metabolism. Therefore, efforts should be made in order to refine the ways we prescribe these drugs, being conventional cytotoxic or newer ones. This program is extremely welcome and may lead to more multi-institutional partnerships and should bring a broader discussion on the use of PGx and pharmacokinetics in routine oncology practice.
RESUMO
Um programa farmacogenética / genômica (PGx) para drogas anticancer está sendo desenvolvido por Kurtz e seu grupo no Instituto Nacional do Câncer (INCA). Pares de droga-gene foram selecionados para o teste de PGx com base na presença de associações de PGx clinicamente validadas e na disponibilidade de diretrizes internacionais com recomendações de dosagem informadas por PGx. Fluoropirimidinas-DPYD, irinotecanoUGT1A1 e tiopurinas-TPMT / NUDT15 foram inicialmente incluídos. A estimativa atual de dosagem da terapia anticâncer geralmente não reflete as complexidades do metabolismo. Portanto, esforços devem ser feitos para refinar as formas de prescrever esses medicamentos, sejam os citotóxicos convencionais como os mais novos. Este programa é extremamente bem-vindo e pode levar a mais parcerias multi-institucionais e deve trazer uma discussão mais ampla sobre o uso de PGx e farmacocinética na prática oncológica.
Keywords:
DPYD - fluoropyrimidines - irinotecan - NUDT15 - pharmacogenomics - thiopurines - TPMT - UGT1A1Descritores:
DPYD - fluoropirimidinas - irinotecano - NUDT15 - farmacogenômica - tiopurinas - TPMT - UGT1A1Publication History
Received: 09 December 2020
Accepted: 19 December 2020
Article published online:
14 May 2021
© 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
Jeziel Basso, Gilberto Schwartsmann. Pharmacogenomic tests in Oncology - finding the right dose. Brazilian Journal of Oncology 2021; 17: e-20210003.
DOI: 10.5935/2526-8732.20210003
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REFERENCES
- Suarez-Kurtz G, Kovaleski G, Elias AB, Motta V, Wolch K, Emerenciano M. et al Implementation of a pharmacogenomic program in a Brazilian public institution. Pharmacogenomics 2020; 21 (08) 549-557
- Reis M, Santoro A, Suarez-Kurtz G.. Thiopurine methyltransferase phenotypes and genotypes in Brazilians. Pharmacogenetics 2003; 13 (06) 371-373
- Relling MV, Schwab M, Whirl-Carrillo M, Suarez-Kurtz G, Pui CH, Stein CM. et al Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clin Pharmacol Ther 2019; 105: 1095-1105
- Suarez-Kurtz G.. Population impact of pharmacogenetic tests in admixed populations across the Americas. Pharmacogenomics J 2020; Oct 27. Epub ahead of print
- Relling MV, Evans WE.. Pharmacogenomics in the clinic. Nature 2015; Oct; 15; 526 (7573) 343-350
- Amstutz U, Henricks LM, Offer SM, Barbarino J, Schellens JHM, Swen JJ. et al Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 2018; 103 (02) 210-216
- Neto OV, Raymundo S, Franzoi MA, do Carmo Artmann A, Tegner M, Müller VV, Hahn RZ, Alves GV, Schwartsmann G, Linden R, Antunes MV. DPD functional tests in plasma, fresh saliva and dried saliva samples as predictors of 5-fluorouracil exposure and occurrence of drug-related severe toxicity. Clin Biochem 2018; Jun; 56: 18-25
- Antunes MV, Raymundo S, Cezimbra da Silva AC, Muller VV, Vicente Neto OJ, Schwartsmann G, Linden R. Determination of Endogenous Concentrations of Uracil and Dihydrouracil in Dried Saliva Spots by LC-MS/MS: Method Development, Validation, and Clinical Application. Ther Drug Monit 2019; Jun; 41 (03) 383-390
- Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M. et al Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 2004; Apr; 15; 22 (08) 1382-1388
- Toffoli G., Cecchin E., Corona G., Russo A., Buonadonna A., D'Andrea M., Pasetto L. M., Pessa S., Errante D., De Pangher V., Giusto M., Medici M., Gaion F., Sandri P., Galligioni E., Bonura S., Boccalon M., Biason P., Frustaci S.. The Role of UGT1A1*28 Polymorphism in the Pharmacodynamics and Pharmacokinetics of Irinotecan in Patients with Metastatic Colorectal Cancer. J. Clin. Oncol 2006; 24 (19) 3061-3068
- Hahn RZ, Antunes MV, Verza SG, Perassolo MS, Suyenaga ES, Schwartsmann G, Linden R.. Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity. Curr Med Chem 2019; 26 (12) 2085-2107
- Hahn R. Z., Arnhold P. C., Andriguetti N. B., Schneider A., Klück H. M., dos Reis S. L., Bastiani M. F., Kael I., da Silva A. C. C., Schwartsmann G., Antunes M. V., Linden R.. Determination of Irinotecan and Its Metabolite SN-38 in Dried Blood Spots Using High-Performance Liquid-Chromatography with Fluorescence Detection. J. Pharm. Biomed. Anal 2018; 150: 51-58
- Jung JA, Lim HS.. Association between CYP2D6 genotypes and the clinical outcomes of adjuvant tamoxifen for breast cancer: a meta-analysis. Pharmacogenomics 2014; 15: 49-60
- Antunes MV, Timm TA, de Oliveira V, Staudt DE, Raymundo S, Gössling G, Biazús JV, Cavalheiro JA, Rosa DD, Wallemacq P, Haufroid V, Linden R, Schwartsmann G.. Influence of CYP2D6 and CYP3A4 Phenotypes, Drug Interactions, and Vitamin D Status on Tamoxifen Biotransformation. Ther Drug Monit 2015; Dec; 37 (06) 733-744