Outcompeting cancer

Abstract

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. This Perspective discusses how cell competition between tumour cells and neighbouring epithelial host cells may dictate tumorigenesis and proposes that manipulating the strength and direction of cell competition could form the basis of an orthogonal therapeutic strategy.