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Therapeutic targeting of the functionally elusive TAM receptor family

Nature Reviews Drug Discovery volume 23, pages 201–217 (2024)Cite this article

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Abstract

The TAM receptor family of TYRO3, AXL and MERTK regulates tissue and immune homeostasis. Aberrant TAM receptor signalling has been linked to a range of diseases, including cancer, fibrosis and viral infections. Specifically, the dysregulation of TAM receptors can enhance tumour growth and metastasis due to their involvement in multiple oncogenic pathways. For example, TAM receptors have been implicated in the epithelial–mesenchymal transition, maintaining the stem cell phenotype, immune modulation, proliferation, angiogenesis and resistance to conventional and targeted therapies. Therapeutically, multiple TAM receptor inhibitors are in preclinical and clinical development for cancers and other indications, with those targeting AXL being the most clinically advanced. Although there has been notable clinical advancement in recent years, challenges persist. This Review aims to provide both biological and clinical insights into the current therapeutic landscape of TAM receptor inhibitors, and evaluates their potential for the treatment of cancer and non-malignant diseases.

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Fig. 1: TAM receptors and their interacting ligands.
Fig. 2: TAM receptor signalling maintains physiological homeostasis.
Fig. 3: The role of TAM receptor signalling in cancer and the action of specific inhibitors.
Fig. 4: GAS6-mediated TAM receptor signalling promotes fibrosis in response to tissue injury.

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Acknowledgements

This work was supported by P01CA257907 (to A.J.G. and E.B.R.) and R01CA272432-01 (to E.B.R.) from the National Cancer Institute (NCI).

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  1. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA

    Yu Rebecca Miao & Erinn B. Rankin

  2. Department of Oncology, University of Oxford, Oxford, UK

    Amato J. Giaccia

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Miao, Y.R., Rankin, E.B. & Giaccia, A.J. Therapeutic targeting of the functionally elusive TAM receptor family. Nat Rev Drug Discov 23, 201–217 (2024). https://doi.org/10.1038/s41573-023-00846-8

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