Cancer cells rely on certain extracellular nutrients to sustain their metabolism and growth. Solute carrier (SLC) transporters enable cells to acquire extracellular nutrients or shuttle intracellular nutrients across organelles. However, the function of many SLC transporters in cancer is unknown. Determining the key SLC transporters promoting cancer growth could reveal important therapeutic opportunities. Here we summarize recent findings and knowledge gaps on SLC transporters in cancer. We highlight existing inhibitors for studying these transporters, clinical trials on treating cancer by blocking transporters, and compensatory transporters used by cancer cells to evade treatment. We propose targeting transporters simultaneously or in combination with targeted therapy or immunotherapy as alternative strategies for effective cancer therapy.
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http://dx.doi.org/10.1038/s41388-023-02593-x | DOI Listing |
J Transl Med
January 2025
Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
Background: Osteosarcoma is the most common malignant bone tumor in children and adolescents, characterized by high disability and mortality rates. Over the past three decades, therapeutic outcomes have plateaued, underscoring the critical need for innovative therapeutic targets. Solute carrier (SLC) family transporters have been implicated in the malignant progression of a variety of tumors, however, their specific role in osteosarcoma remains poorly understood.
View Article and Find Full Text PDFNat Commun
January 2025
Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis.
View Article and Find Full Text PDFMol Inform
January 2025
Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstr. 48, 48149, Muenster, Germany.
Primary carnitine deficiency (PCD) is a rare autosomal recessive genetic disorder caused by missense mutations in the SLC22A5 gene encoding the organic carnitine transporter novel type 2 (OCTN2). This study investigates the structural consequences of PCD-causing mutations, focusing on the N32S variant. Using an alpha-fold model, molecular dynamics simulations reveal altered interactions and dynamics suggesting potential mechanistic changes in carnitine transport.
View Article and Find Full Text PDFBackground And Aim: The high rate of tumor growth results in an increased need for amino acids. As solute carriers (SLC) transporters are capable of transporting different amino acids, cancer may develop as a result of these transporters' over-expression due to their complex formation with other biological molecules. Therefore, this review investigated the role of SLC transporters in the progression of cancer.
View Article and Find Full Text PDFLeuk Lymphoma
January 2025
Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Solute carrier (SLC) transporters play a crucial role in facilitating the cellular uptake of various anticancer drugs, such as methotrexate (MTX). This study aimed to analyze the impact of nonsynonymous single nucleotide polymorphisms (SNPs) in , , and on MTX exposure, toxicities, and prognosis in 148 patients with acute lymphoblastic leukemia (ALL). The rs7311358 polymorphism was significantly associated with the median dose-normalized MTX concentrations at 24 h ( < .
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