Solute Carrier Transporters in Cancer Therapeutics
Summary
Solute carrier (SLC) transporters constitute a vast superfamily of membrane proteins responsible for the regulated movement of amino acids, nucleotides, ions and drugs across cellular membranes. In cancer, altered SLC expression underpins the metabolic rewiring that fuels rapid proliferation and supports survival under nutrient-deprived conditions. Beyond supplying essential metabolites, certain SLCs facilitate the uptake of chemotherapeutic agents and targeted therapies, thereby shaping drug efficacy and resistance. Recent advances in structural biology and functional genomics have illuminated the molecular basis of substrate recognition and transporter regulation, enabling the design of inhibitors or modulators to exploit tumour-specific transporter dependencies. Consequently, SLCs have emerged both as biomarkers to stratify patients and as therapeutic targets to overcome chemoresistance, opening new avenues for precision oncology.
Research from Nature Portfolio
Recent studies have applied genome-wide CRISPR interference and activation screening to delineate the landscape of nutrient transport in cancer cells across diverse microenvironments. This approach revealed context-dependent roles for amino acid and glucose transporters in sustaining proliferation, identified serotonin uptake as a key suppressor of ferroptosis under cystine starvation, and highlighted transporters whose inhibition curtails tumour growth in vivo. Complementing these functional insights, high-resolution cryo-electron microscopy of an SLC transporter unveiled dynamic substrate-binding pockets and conformational states, providing a structural blueprint for rational design of selective inhibitors that may be repurposed to disrupt nutrient supply in cancer cells.
Solute Carrier Transporters in Cancer Therapeutics publication trend
The graph below shows the total number of articles in solute carrier transporters in cancer therapeutics across all publications each year (not limited to Nature Index journals).
Technical terms
Solute carrier (SLC) transporter: Membrane proteins mediating uptake and efflux of metabolites, ions and drugs.
CRISPR interference/activation (CRISPRi/a): A screening technique that represses or activates gene expression to determine functional roles.
Ferroptosis: Iron-dependent regulated cell death driven by lipid peroxidation.
Mitophagy: Selective autophagic removal of damaged mitochondria to maintain cellular homeostasis.
Tumour microenvironment: The cellular and molecular milieu surrounding cancer cells, influencing growth and therapy response.
Precision oncology: A therapeutic paradigm that matches treatments to individual tumour characteristics, including transporter profiles.
References
- A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments. Nature Cell Biology (2024).
- Substrate binding plasticity revealed by Cryo-EM structures of SLC26A2. Nature Communications (2024).
- SLC5A3 depletion promotes apoptosis by inducing mitochondrial dysfunction and mitophagy in gemcitabine-resistant pancreatic cancer cells. Cell Death & Disease (2025).
- Emerging roles of the solute carrier family in pancreatic cancer. Clinical and Translational Medicine (2021).
- Harnessing Solute Carrier Transporters for Precision Oncology. Molecules (2017).
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