Patients’ genetic makeup may be important for the safety and pharmacokinetics of imatinib, according to a new study published in the journal Drug Metabolism and Pharmacokinetics. Following validation in larger studies, this finding may serve as fundamental knowledge for imatinib therapy.

Imatinib is sold under the brand name Gleevec® and is used to treat many types of cancers including gastrointestinal stromal tumors (GISTs). However, there are marked differences between patients in terms of imatinib efficacy and toxicity.

Research has shown that these differences are related to genetic polymorphisms among individuals. Here, a team of researchers led by Tatsuo Kanda, MD, PhD, evaluated the impacts of genetic polymorphisms on the incidences of adverse events and trough plasma concentrations of imatinib focusing on patients from Japan with GISTs.

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The team genotyped 35 candidate single nucleotide polymorphisms (SNPs) in genes encoding for drug-metabolizing enzymes and transporters in 65 patients with GISTs from Japan.

They found that 421C>A in the ABCG2 gene was significantly associated with higher incidence rates of grade 2 rashes or higher. This gene encodes the adenosine triphosphate-binding cassette superfamily G member 2 protein, for which imatinib is a substrate.

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The researchers also found that 5 SNPs were associated with significant trends toward higher or lower dose-adjusted through plasma concentrations.

Using statistical analysis, the researchers demonstrated that 334T>G in the SLCO1B3 gene encoding organic anion transporting polypeptide 1B3 and 1032G>A in the SLCO1A2 gene encoding solute carrier organic anion transporter family member 1A2 significantly contributed to the individual variability of trough plasma concentrations.

The proteins encoded by these 2 genes both play a role in the cellular uptake of organic ions in the liver. “Genetic variations in ABCG2, SLCO1B3, and SLCO1A2 may play important roles in the safety and pharmacokinetics of imatinib in Japanese patients with GIST,” the researchers wrote. “Although a replication study is necessary.”


Maekawa K, Yamamura M, Matsuki A, et al. Impacts of SNPs on adverse events and trough concentration of imatinib in patients with gastrointestinal stromal tumors. Drug Metab Pharmacokinet. Published online December 22, 2021. doi:10.1016/j.dmpk.2021.100441