Organic Anion Transporting Polypeptides in Cancer: Biological Roles and Therapeutic Modulation

Organic anion transporting polypeptides (OATPs) are membrane proteins responsible for the cellular uptake of numerous endogenous molecules and clinically important drugs, thereby playing a pivotal role in drug pharmacokinetics. These transporters are especially relevant for the intracellular delivery of several anticancer agents, including methotrexate, taxane and camptothecin derivatives, as well as imatinib. OATPs display distinct tissue-specific distributions, and their expression levels and subcellular localization are frequently dysregulated in various malignancies, influencing tumor responsiveness to chemotherapeutic treatment. The cancer-associated expression patterns and limited presence of several OATPs in healthy tissues suggest their potential as targets for tumor-specific therapeutic strategies. Regulation of OATPs expression is influenced by multiple mechanisms, including activation of nuclear receptor signaling, epigenetic regulation, post-translational modifications, and alterations in membrane lipid composition, all of which can affect transporter function and localization. In this review, we summarize current approaches for modulating OATPs expression, with particular emphasis on therapeutic strategies designed to promote transporter retention at the plasma membrane.