There is a large gap between the deep understanding of mechanisms driving tumour growth and the reasons why patients ultimately die of cancer. It is now appreciated that interactions between the tumour and surrounding non-tumour (sometimes referred to as host) cells play critical roles in mortality as well as tumour progression, but much remains unknown about the underlying molecular mechanisms, especially those that act beyond the tumour microenvironment. Drosophila has a track record of high-impact discoveries about cell-autonomous growth regulation, and is well suited to now probe mysteries of tumour – host interactions. Here, we review current knowledge about how fly tumours interact with microenvironmental stroma, circulating innate immune cells and distant organs to influence disease progression. We also discuss reciprocal regulation between tumours and host physiology, with a particular focus on paraneoplasias. The fly’s simplicity along with the ability to study lethality directly provide an opportunity to shed new light on how cancer actually kills.
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The authors thank D. Raulet and K. Evason for sharing expertise, and C. Liu, R. Boileau, A. Figueroa-Clarevega, A. Houser, S. Haraguchi and S. Zhou for important contributions to tumour–host work in the Bilder laboratory. This work has been supported by National Institutes of Health (NIH) grants GM130388, GM090150 and R21CA180107 to D.B., a University of California Cancer Research Coordinating Fellowship to T.-C.H. and a Mark Foundation Damon Runyon Fellowship (DRG 2400-20) to K.O. The authors acknowledge the superb and influential work of the late M. Vidal, a pioneer in the field.
The authors declare no competing interests.
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A signalling molecule produced by a tumour that is an effector of interactions with a host.
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Bilder, D., Ong, K., Hsi, TC. et al. Tumour–host interactions through the lens of Drosophila. Nat Rev Cancer 21, 687–700 (2021). https://doi.org/10.1038/s41568-021-00387-5
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