Evolvable signaling networks of receptor tyrosine kinases: Relevance of robustness to malignancy and to cancer therapy

Ido Amit, Ron Wides, Yosef Yarden

Research output: Contribution to journalReview articlepeer-review

118 Scopus citations

Abstract

Robust biological signaling networks evolved, through gene duplications, from simple, relatively fragile cascades. Architectural features such as layered configuration, branching and modularity, as well as functional characteristics (e.g., feedback control circuits), enable fail-safe performance in the face of internal and external perturbations. These universal features are exemplified here using the receptor tyrosine kinase (RTK) family. The RTK module is richly mutated and overexpressed in human malignancies, and pharmaceutical interception of its signaling effectively retards growth of specific tumors. Therapy-induced interception of RTK-signaling pathways and the common evolvement of drug resistance are respectively considered here as manifestations of fragility and plasticity of robust networks. The systems perspective we present views pathologies as hijackers of biological robustness and offers ways for identifying fragile hubs, as well as strategies to overcome drug resistance.

Original languageEnglish
Article number151
JournalMolecular Systems Biology
Volume3
DOIs
StatePublished - 2007

Keywords

  • Cancer therapy
  • Evolvability
  • Feedback control
  • Growth factor
  • Oncogene
  • Receptor tyrosine kinase
  • Robustness

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