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Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk

Acta Pharmacologica Sinica (2026) Cite this article

Abstract

The tumor microenvironment (TME) is a metabolically dynamic niche characterized by active metabolic crosstalk between tumor cells and various stromal and immune cell subsets, which critically influences tumor progression and therapeutic outcomes. Within this ecosystem, solute carrier (SLC) transporters are gatekeepers that mediate the transport of a wide range of metabolites, including nutrients, ions, and signaling molecules, across cellular membranes. SLC transporters have emerged as active regulators of TME composition and intercellular communication, representing promising yet underexplored therapeutic targets in cancer. This review highlights the central role of SLC transporters in orchestrating the competitive uptake of nutrients and the exchange of oncometabolites, thereby modulating immune responses, angiogenesis, and metabolic adaptation in the TME. By outlining strategies targeting SLC transporters for cancer therapy, this review also underscores the emerging potential of SLC transporters as therapeutic targets and offers a renewed perspective on targeting TME metabolism.

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Fig. 1: SLC transporter-mediated nutrient competition between tumor cells and immune cells in the TME.
The alternative text for this image may have been generated using AI.
Fig. 2: SLC-mediated exchange of oncometabolites within the TME.
The alternative text for this image may have been generated using AI.
Fig. 3: Engineering SLC transporters to reprogram metabolism in CAR-T cells.
The alternative text for this image may have been generated using AI.

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Acknowledgements

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB0830000), Natural Science Foundation of China (82225046, 22337004), National Key Research and Development Project of China (2024YFC2815904), Innovative Drug Research and Development National Science and Technology Major Project (2025ZD1804100), Science and Technology Commission of Shanghai Municipality (YDZX20233100004032), and Key R&D Program of Shandong Province (2024CXPT028, 2025CXPT011).

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Authors and Affiliations

  1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 201203, China

    Zi-han Zhang, Zi-yi Ding, Luo-yi Chen, Yi-xian Fu & Min Huang

  2. Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, 264117, China

    Min Huang

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  1. Zi-han Zhang
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  2. Zi-yi Ding
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  3. Luo-yi Chen
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  4. Yi-xian Fu
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Contributions

ZHZ drafted the original manuscript and contributed to the literature search, ZYD prepared the figures, LYC did the English language editing, YXF and MH conceptualized and supervised the work. All authors reviewed and approved the manuscript.

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Correspondence to Yi-xian Fu or Min Huang.

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Zhang, Zh., Ding, Zy., Chen, Ly. et al. Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk. Acta Pharmacol Sin (2026). https://doi.org/10.1038/s41401-026-01815-8

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