Pharmacogenetics of Thiopurines

Overview

Journal Cancer Drug Resist

Date 2022 May 18

PMID 35582727

Authors

Raffaella Franca

Giulia Zudeh

Sofia Pagarin

Marco Rabusin

Marianna Lucafo

Gabriele Stocco

Giuliana Decorti

Affiliations

Soon will be listed here.

Abstract

Polychemotherapeutic protocols for the treatment of pediatric acute lymphoblastic leukemia (ALL) always include thiopurines. Specific approaches vary in terms of drugs, dosages and combinations. Such therapeutic schemes, including risk-adapted intensity, have been extremely successful for children with ALL who have reached an outstanding 5-year survival of greater than 90% in developed countries. Innovative drugs such as the proteasome inhibitor bortezomib and the bi-specific T cell engager blinatumomab are available to further improve therapeutic outcomes. Nevertheless, daily oral thiopurines remain the backbone maintenance or continuation therapy. Pharmacogenetics allows the personalization of thiopurine therapy in pediatric ALL and clinical guidelines to tailor therapy on the basis of genetic variants in and genes are already available. Other genes of interest, such as and , have been implicated in interindividual variability in thiopurines efficacy and adverse effects and need additional research to be implemented in clinical protocols. In this review we will discuss current literature and clinical guidelines available to implement pharmacogenetics for tailoring therapy with thiopurines in pediatric ALL.

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