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Untangling the web of intratumour heterogeneity

Abstract

Intratumour heterogeneity (ITH) is a hallmark of cancer that drives tumour evolution and disease progression. Technological and computational advances have enabled us to assess ITH at unprecedented depths, yet this accumulating knowledge has not had a substantial clinical impact. This is in part due to a limited understanding of the functional relevance of ITH and the inadequacy of preclinical experimental models to reproduce it. Here, we discuss progress made in these areas and illuminate future directions.

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Fig. 1: Cell-autonomous and non-cell-autonomous sources of ITH.
Fig. 2: Clonality, adaption and progression of heterogeneous tumours.

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Acknowledgements

We thank A. Marusyk (Moffit Cancer Center) and members of our laboratory for critical reading of the manuscript and helpful suggestions. The authors are funded by the National Cancer Institute R35 CA197623 (K.P.) and EMBO (M.S.).

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Correspondence to Kornelia Polyak.

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K.P. serves on the Scientific Advisory Board of Acrivon Therapeutics, Vividion Therapeutics, Scorpion Therapeutics and the Novartis Institute for BioMedical Research, holds equity options in Scorpion Therapeutics, is a consultant to Aria Pharmaceuticals, received honorarium from AstraZeneca and New Equilibrium Biosciences, and has an institutional research agreement with Novartis. The remaining authors declare no competing interests.

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Li, Z., Seehawer, M. & Polyak, K. Untangling the web of intratumour heterogeneity. Nat Cell Biol 24, 1192–1201 (2022). https://doi.org/10.1038/s41556-022-00969-x

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