The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy

Abstract

Transporter-mediated drug resistance is a major obstacle in anticancer drug delivery and a key reason for cancer drug therapy failure. Membrane solute carrier (SLC) transporters play a crucial role in the cellular uptake of drugs. The expression and function of the SLC transporters can be down-regulated in cancer cells, which limits the uptake of drugs into the tumor cells, resulting in the inefficiency of the drug therapy. In this review, we summarize the current understanding of low-SLC-transporter-expression-mediated drug resistance in different types of cancers. Recent advances in SLC-transporter-targeting strategies include the development of transporter-utilizing prodrugs and nanocarriers and the modulation of SLC transporter expression in cancer cells. These strategies will play an important role in the future development of anticancer drug therapies by enabling the efficient delivery of drugs into cancer cells.

Targeting Solute Carrier Transporters (SLCs) as a Therapeutic Target in Different Cancers

“…Transporters play an important role in the modulation of metabolism and ion homeostasis of tumor cells, both important factors in proliferation, apoptosis, hypoxia, and migration [ 15 ]. SLC transporters represent a plethora of new therapeutic targets for rare diseases and many metabolic disorders by being amenable to targeting small molecules [ 11 , 17 ]. Importantly, many SLC transporters are expressed on the cell surface and therefore could be targeted by small molecules and therapeutic antibodies [ 15 , 131 ].…”

“…SLC transporters facilitate the entry of diverse metabolically significant substrates into cells, which is essential for human physiology. These processes include glucose absorption, uptake of water-soluble vitamins crucial for vital functions, transportation of metal ions, amino acid intake in the intestine, and reabsorption of neurotransmitters into presynaptic neurons [ 11 ]. Tumorigenesis, a complex process, orchestrates the conversion of normal cells into highly malignant derivatives [ 12 , 13 ].…”

“…In this mechanism, the transport domain binds the substrate and undergoes rigid body movement to translocate across the membrane, ultimately releasing the substrate [ 10 ]. In a recent article by Puris et al and Lin et al [ 11 , 12 ], the therapeutic potential of SLC transporters in cancer was explored. It was posited that the expression of SLCs is diminished in cancerous cells, potentially leading to compromised drug delivery [ 12 ], although this phenomenon remains relatively understudied.…”

Gastric cancer with brain metastasis: from molecular characteristics and treatment

“…A number of studies using brain metastasis mouse models have shown that the heterogeneity of the BTB significantly affects the concentration and distribution of drugs in the tumor ( 53 ). Currently, clinical treatment methods and strategies are actively being developed to promote the bypass of drugs through the brain barrier and improve drug penetration and increase blood concentration in the brain ( 54 ).…”

Enhanced imatinib uptake through influx transporters and its quantification based on LC-MS/MS in human leukemic cells

“…OCT1 is mainly involved in the hepatic uptake of various drugs, toxins, and endogenous substrates [9][10][11][12]. Similarly, OATP1A2 is also involved in the transport of a wide variety of xenobiotics including anticancer drugs and endogenous substrates [13]. These transporters regulate the in ux of substrates through electrochemical gradients across the membrane [7].…”