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Tumour heterogeneity and cancer cell plasticity

Abstract

Phenotypic and functional heterogeneity arise among cancer cells within the same tumour as a consequence of genetic change, environmental differences and reversible changes in cell properties. Some cancers also contain a hierarchy in which tumorigenic cancer stem cells differentiate into non-tumorigenic progeny. However, it remains unclear what fraction of cancers follow the stem-cell model and what clinical behaviours the model explains. Studies using lineage tracing and deep sequencing could have implications for the cancer stem-cell model and may help to determine the extent to which it accounts for therapy resistance and disease progression.

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Figure 1: Cancer cell fate versus potential.
Figure 2: Hierarchy of tumour cells.
Figure 3: Predictions of transplantation and therapy response depend on the form of cell plasticity.
Figure 4: Tumorigenic cells cannot recapitulate the heterogeneity of tumours with extensive genetic heterogeneity.
Figure 5: Clonal evolution and tumorigenic cell differentiation can independently or jointly contribute to tumour heterogeneity.
Figure 6: Genetic changes and the inherent properties of tumorigenic cells can each contribute to therapy resistance.

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Acknowledgements

This work was supported by the Howard Hughes Medical Institute and the Cancer Prevention and Research Institute of Texas. We apologize to authors whose papers could not be cited owing to space restrictions.

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Correspondence to Sean J. Morrison.

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S.J.M was a founder and is a stockholder in OncoMed Pharmaceuticals.

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Meacham, C., Morrison, S. Tumour heterogeneity and cancer cell plasticity. Nature 501, 328–337 (2013). https://doi.org/10.1038/nature12624

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