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The ERBB network: at last, cancer therapy meets systems biology

Abstract

Although it is broadly agreed that the improved treatment of patients with cancer will depend on a deeper molecular understanding of the underlying pathogenesis, only a few examples are already available. This Timeline article focuses on the ERBB (also known as HER) network of receptor tyrosine kinases (RTKs), which exemplifies how a constant dialogue between basic research and medical oncology can translate into both a sustained pipeline of novel drugs and ways to overcome acquired treatment resistance in patients. We track the key early discoveries that linked this RTK family to oncogenesis, the course of pioneering clinical research and their merger into a systems-biology framework that is likely to inspire further generations of effective therapeutic strategies.

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Figure 1: Family portrait: functional and structural features that are unique to each receptor.
Figure 2: ERBB mutations in cancer.
Figure 3: Drug flood: antibodies and small molecules intercepting ERBB signalling.

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Acknowledgements

The authors would like to thank M. Eisenstein, M. Feldman, Y. Mosesson, S. Lavi, W. Koestller and G. Tarcic for their help. They apologize to those colleagues whose work is not cited owing to space limitations. The authors' research is funded by the US National Cancer Institute, the European Research Council, the Seventh Framework Program of the European Commission, the German–Israeli Project Cooperation (DIP), the Israel Cancer Research Fund and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Y.Y. is the incumbent of the Harold and Zelda Goldenberg Professorial Chair.

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Yarden, Y., Pines, G. The ERBB network: at last, cancer therapy meets systems biology. Nat Rev Cancer 12, 553–563 (2012). https://doi.org/10.1038/nrc3309

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