The Role of Transporters in Future Chemotherapy
Keywords:ATP-binding cassette (ABC), L-type amino acid transporter 1 (LAT1), multidrug resistance (MDR), prodrug, solute carrier (SLC)
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.
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