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Nutrient transporters: connecting cancer metabolism to therapeutic opportunities

Oncogene volume 42, pages 711–724 (2023)Cite this article

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Abstract

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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Fig. 1: Metabolite transporters and their functions.
Fig. 2: Inhibitors of metabolite transporters.
Fig. 3: Strategies for identifying and exploiting transporters required by cancer.

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Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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Acknowledgements

ZCN was supported by the Michigan Postdoctoral Pioneer Program at the University of Michigan Medical School, NIH/NCI grant K99CA267176 and NIH/NIGMS grant R25GM143298. MP was supported by NIH/NCI grants R01CA151588 and R01CA198074. CAL was supported by the NIH/NCI grants R37CA237421, R01CA248160, and R01CA244931, and MP and CAL by UMCCC Core Grant (P30CA046592). SEK was supported by the National Research Foundation of Korea (NRF) grant (2020R1C1C1013220). The funders had no role in the content and publication of this manuscript. The authors apologize to researchers whose relevant work could not be cited in this review due to space limitations.

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Authors and Affiliations

  1. Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

    Zeribe Chike Nwosu & Costas A. Lyssiotis

  2. Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA

    Zeribe Chike Nwosu & Costas A. Lyssiotis

  3. Department of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul, 02841, Republic of Korea

    Mun Gu Song & Sung Eun Kim

  4. Department of Integrated Biomedical and Life Sciences, College of Health Sciences, Korea University, Seoul, 02841, Republic of Korea

    Mun Gu Song & Sung Eun Kim

  5. Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Marina Pasca di Magliano

  6. Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA

    Costas A. Lyssiotis

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  1. Zeribe Chike Nwosu
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ZCN and SEK conceived and wrote the original draft and drew the figures. MGS, MP, and CAL contributed to the critical revision of the manuscript and approved the submitted version.

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Correspondence to Sung Eun Kim.

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Competing interests

CAL has received consulting fees from Astellas Pharmaceuticals, Odyssey Therapeutics, and T-Knife Therapeutics, and is an inventor on patents pertaining to Kras regulated metabolic pathways, redox control pathways in pancreatic cancer, and targeting the GOT1-pathway as a therapeutic approach (US Patent No: 2015126580-A1, 05/07/2015; US Patent No: 20190136238, 05/09/2019; International Patent No: WO2013177426-A2, 04/23/2015). Other authors declare no competing interests.

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Nwosu, Z.C., Song, M.G., di Magliano, M.P. et al. Nutrient transporters: connecting cancer metabolism to therapeutic opportunities. Oncogene 42, 711–724 (2023). https://doi.org/10.1038/s41388-023-02593-x

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