R2.3: Multistep Nature Of Carcinogenesis

Activation of a single oncogene is not sufficient to cause cancer, as is loss of a single allele for a tumour suppressor gene. It is thought that tumour development is the combination of numerous small steps, which must occur in some order, before a cancer can emerge. This is supported by numerous studies, knowledge of the function of oncogenes and tumour suppressor genes, as well as the genes and proteins involved in immortality, evasion of apoptosis, angiogenesis and metastasis.

The Vogelstein Model of Multistep Carcniogenesis

The first published model of a multistep carcinogenesis based on molecular changes was published in the 1980s by Vogelstein (although I have heard debate about who actually postulated this first). In this model, colon cancer develops along a series of steps, from normal epithelium, hyperplasia, adenoma and eventually carcinoma. Each step is associated with the mutation of additional genes.