Pharmacogenomics is a fast-growing field of personalized medicine using a patient's genomic profile to determine drug disposition or response to drug therapy, in order to develop safer and more effective pharmacotherapy. Childhood acute lymphoblastic leukemia (ALL), being the most common malignancy in childhood, which is treated with uniform and standardized clinical trials, is remarkably poised for pharmacogenomic studies. In the last decade, unbiased genome-wide association studies have identified multiple germline risk factors that strongly modify host response to drug therapy. Some of these genomic associations (e.g. TPMT, NUDT15 and mercaptopurine dosing) have accumulated a significant level of evidence on their clinical utility such that they are warranted as routine clinical tests to guide modification of treatment. Most of these germline associations however, have not yet reached such actionability. Insights have also been gathered on germline factors that affect host susceptibility to adverse effects of antileukemic agents (eg, vincristine, asparaginase, methotrexate). Further large-scale studies are required, along with the assimilation of both germline and somatic variants, to precisely predict host drug response and drug toxicities, with the eventual aim of executing genomic-based precision-pharmacotherapy in the treatment of ALL.
Keywords: ALL; Acute; Leukemia; Lymphoblastic; MRD; Pharmacogenomics; Response; Toxicity.
Copyright © 2017 Elsevier Ltd. All rights reserved.