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Drug-resistant epilepsy (DRE), characterized by recurrent seizures despite the administration of multiple antiseizure medications (ASMs), poses a substantial challenge in epilepsy management. One of the primary difficulties in managing DRE lies in the absence of reliable biomarkers for identifying patients at risk. The pathomechanism underlying the acquisition of pharmacoresistance in epilepsy remains elusive, although several hypotheses have been proposed, including network degeneration, neuroinflammation, changes in pharmacokinetics and pharmacodynamics, and genetic and/or epigenetic alterations in drug transporters [1,2].