Exploratory study of the use of p-glycoprotein inhibitors in therapy in animals with oncological pathologies

ATP binding cassette (ABC) transporters are a group of proteins whose function is to transport nutrients into the cell and excretion endogenous and exogenous molecules from the cell. The ABCB1(MDR1) gene encodes P-glycoprotein (P-gp), a cellular membrane pump. P-glycoprotein mediated drug transport is present in more places (including the blood brain barrier). P-gp also regulates intestinal absorption. The ABCB1 gene and the P-glycoprotein encoded by it are also responsible for the formation of multidrug resistance (MDR). P-glycoprotein dysfunction can occur both as resulting from neoplasia and as resulting from drug-drug interactions in dog or cat. This makes it relevant to study the mechanisms of MDR formation in animals undergoing cancer therapy, as well as to find effective ways to prevent and reduce MDR. One of the options to increase the effectiveness of cancer therapy and improve the survival of animals, including relapses, metastases and unresectable tumors, is the inclusion of ABC transporter inhibitors in treatment protocols. One of the substances that are considered as inhibitors of ABS transporters is quercetin— a natural biochemical substance of the flavonoid group. In the period from 2024 to 2025, in order to assess the feasibility of further studying the use of quercetin as an inhibitor of the multidrug efflux transporter ABCB1 (MDR1) in animals undergoing cancer therapy, we conducted an exploratory study. The animals included in the study were treated with toceranib, imatinib, sorafenib, lapatinib and trametinib. The biologically active substance dihydroquercetin was used as an adjuvant at a dose of 2-10 mg/kg/24 hours per os. The results of our exploration study confirm the need for clinical studies of the use of quercetin as ABCB1 (MDR1) transporter inhibitor in animals undergoing cancer therapy.

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