The tumour microenvironment plays a critical role in determining tumour fate. Within that environment, and indeed throughout epithelial tissues, cells experience competition with their neighbours, with those less fit being eliminated by fitter adjacent cells. Herein we discuss evidence suggesting that mutations in cancer cells may be selected for their ability to exploit cell competition to kill neighbouring host cells, thereby facilitating tumour expansion. In some instances, cell competition may help host tissues to defend against cancer, by removing neoplastic and aneuploid cells. Cancer risk factors, such as high-sugar or high-fat diet and inflammation, impact cell competition-based host defences, suggesting that their effect on tumour risk may in part be accounted for by their influence on cell competition. We propose that interventions aimed at modifying the strength and direction of cell competition could induce cancer cell killing and form the basis for novel anticancer therapies.
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The authors thank the reviewers for their constructive and thorough reviews that greatly helped to shape the manuscript. The authors thank P. Langton for critical reading and Y. Fujita for constructive criticism of the manuscript. The authors apologize for any studies that they were unable to cite owing to space limitations. Work in the Piddini laboratory is funded by a Wellcome Trust Senior Research Fellowship (grant 205010/Z/16/Z), by a Programme Foundation Award from Cancer Research UK (grant C38607/A26831) and by a start-up fund from the University of Bristol.
The authors declare no competing interests.
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Vishwakarma, M., Piddini, E. Outcompeting cancer. Nat Rev Cancer 20, 187–198 (2020). https://doi.org/10.1038/s41568-019-0231-8