Contribution of organic cation-type transporters to chemotherapy-induced toxicities

Membrane transporters are integral proteins contributing to the cellular integrity of all tissue and cell types. The solute carrier superfamily represents the second largest family of membrane proteins, encoding for over 400 transport proteins that collectively, play a pivotal role in cellular homeostasis, including the transport of essential nutrients or ions and the removal of toxic by-products. Moreover, membrane transporters are major contributors to the pharmacokinetics of therapeutic drugs, and the tissue specific expression of uptake transporters can serve as initiating mechanisms that govern a drug’s pharmacodynamic properties (e.g., efficacy and toxicity). Here, we demonstrate that the sub-family of organic cation transporters are critical mediators initiating the debilitating toxicity profiles of chemotherapeutic agents, and that the targeting of these transporters can be exploited clinically to afford protection against injury in healthy tissues without compromising therapeutic benefits.