Tumour formation involves the co-evolution of neoplastic cells together with extracellular matrix, tumour vasculature and immune cells. Successful outgrowth of tumours and eventual metastasis is not determined solely by genetic alterations in tumour cells, but also by the fitness advantage such mutations confer in a given environment. As fitness is context dependent, evaluating tumours as complete organs, and not simply as masses of transformed epithelial cells, becomes paramount. The dynamic tumour topography varies drastically even throughout the same lesion. Heterologous cell types within tumours can actively influence therapeutic response and shape resistance.
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We would like to express our gratitude to P. Bishop, T. Junttila, K. Leong, J. Settleman, W. Ye, J. Low and S. Scales for their critical review of the manuscript. We also thank the reviewers for valuable insight and suggestions. Our sincere apologies go to authors whose work we are unable to cite due to space limitations.
The authors are employees of Genentech Inc. and own shares in Roche.
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Junttila, M., de Sauvage, F. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501, 346–354 (2013). https://doi.org/10.1038/nature12626
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