Recent advances in research on multistage tumorigenesis

Br J Cancer. 2000 Jul;83(1):1-5. doi: 10.1054/bjoc.2000.1309.


Tumour development is a multi-step process during which genetic and epigenetic events determine the transition from a normal to a malignant cellular state. In the past decade, extensive effort has been made not only to define the molecular mechanisms underlying progression to malignancy but also to predict the development of the disease and to identify possible molecular targets for therapy. Common to most tumours, several regulatory circuits are altered during multistage tumour progression, most importantly, the control of proliferation, the balance between cell survival and programmed cell death (apoptosis), the communication with neighbouring cells and the extracellular matrix, the induction of tumour neovascularization (angiogenesis) and, finally, tumour cell migration, invasion and metastatic dissemination. De-regulation of each of these processes represents a rate-limiting step for tumour development and, hence, has to be achieved by tumour cells in a highly selective manner during tumour progression. In this review we summarize recent advances in cancer research that have provided new insights in the molecular mechanisms underlying the transition between one tumour stage and the next and into their concerted action during tumour progression. Cultured human tumour cell lines as well as transgenic and knock-out mouse models of tumorigenesis have been instrumental in these experimental approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Differentiation
  • Cell Division
  • Cell Transformation, Neoplastic* / genetics
  • Cell Transformation, Neoplastic* / pathology
  • Cellular Senescence
  • DNA Repair / genetics
  • Disease Progression
  • Genes, Tumor Suppressor
  • Genetic Predisposition to Disease
  • Growth Substances / physiology
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / etiology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / physiopathology
  • Oncogenes
  • Phenotype
  • Signal Transduction


  • Growth Substances