The expression of membrane transporter is often altered in cancer cells compared to their corresponding healthy cells. Since these proteins, classified into solute carriers (SLCs) and ATP-binding cassettes (ABCs), can carry not only endogenous compounds, nutrients, and metabolites, but also drugs across the cell membranes, they have a crucial role in drug exposure and clinical outcomes of chemotherapeutics. Curiously, up-regulation of SLCs can be exploited to deliver chemotherapeutics, their prodrugs, and diagnostic radio-tracers to gain cancer cell-selective targeting, as exemplified with L-type amino acid transporter 1 (LAT1). SLCs can also be inhibited to limit the nutrient uptake of cancer cells and thus, cell growth and proliferation. Furthermore, LAT1 can be utilized to deliver ABC-inhibitors selectively into the cancer cells to block the efflux of other chemotherapeutics suffering from acquired or intrinsic efflux transport-related multidrug resistance (MDR). Taking into account the current literature, compounds that can affect transporter up- or down-regulation of transporters in a cancer cell-selective manner could be a valuable tool and promising chemotherapy form in the future.
Keywords: ATP-binding cassette (ABC); L-type amino acid transporter 1 (LAT1); multidrug resistance (MDR); prodrug; solute carrier (SLC).
Copyright 2022 Johanna Huttunen, Kristiina M. Huttunen. License: This work is licensed under a Creative Commons Attribution 4.0 International License.