Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs

Our understanding of the solute carrier (SLC) family of transporters has greatly increased in recent years, especially in oncology, and a wealth of information is now available, indicating that certain SLC family members contribute to the cellular accumulation of small-molecule cancer drugs at sites of injury and to unwanted toxicity in normal tissues. The present review aimed to provide an overview of the toxic effects of commonly used chemotherapy drugs that are associated with SLC-mediated transport, how these associations have been derived, what ensuing intervention strategies have been explored, and how the investigation of these phenomena might change in the near future with the availability of increasingly sophisticated and innovative models and techniques. It is expected that this rapidly emerging field continues to contribute to filling our gaps in knowledge and will aid in the development of interventions aimed at preventing debilitating side effects of cancer drugs and improving the quality of life. SIGNIFICANCE STATEMENT: Toxicities associated with small-molecule chemotherapeutics can be debilitating or even life-threatening and pose a burden on the healthcare system. Improving our understanding of the initiating transporter-mediated mechanisms of these side effects is crucial to the development of preventative or treatment strategies.