Pharmacogenetics of thiopurines

Raffaella Franca; Giulia Zudeh; Sofia Pagarin; Marco Rabusin; Marianna Lucafò; Gabriele Stocco; Giuliana Decorti

doi:10.20517/cdr.2019.004

Pharmacogenetics of thiopurines

Cancer Drug Resist. 2019 Jun 19;2(2):256-270. doi: 10.20517/cdr.2019.004. eCollection 2019.

Authors

Raffaella Franca¹, Giulia Zudeh^{2

3}, Sofia Pagarin⁴, Marco Rabusin⁴, Marianna Lucafò^{4

5}, Gabriele Stocco³, Giuliana Decorti^{1

4}

Affiliations

¹ Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34127, Italy.
² PhD Course in Reproductive and Developmental Sciences, University of Trieste, Trieste 34127, Italy.
³ Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
⁴ Institute for Maternal and Child Health I.R.C.C.S. Burlo Garofolo, Trieste 34127, Italy.
⁵ Experimental and Clinical Pharmacology Unit, Centro di riferimento oncologico, I.R.C.C.S., Aviano 33081, Italy.

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 TPMT and NUDT15 genes are already available. Other genes of interest, such as ITPA and PACSIN2, 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.

Keywords: NUDT15; PACSIN2; Thiopurines; acute lymphoblastic leukemia; inosine triphosphate pyrophosphatase; pharmacogenetics clinical implementation; therapy personalization; thiopurine methyltransferase.

Publication types

Review