Influence of tumour micro-environment heterogeneity on therapeutic response

Nature. 2013 Sep 19;501(7467):346-54. doi: 10.1038/nature12626.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / pathology
  • Disease Progression
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Tumor Microenvironment* / drug effects
  • Tumor Microenvironment* / physiology