The major ‘drivers’ of cancer development arise in pathways from receptor tyrosine kinases that ultimately control cell division. Thus, for example, aberrant activity of the RAS-MAPK pathway occurs frequently across a broad spectrum of cancer types. However, cancer-promoting mutations occur in other signalling pathways and, as we have seen, all aspects of cellular behaviour are ultimately affected. The molecular details of most of these pathways and how they can be subverted in cancers are now well established. The integration between diverse pathways creates a picture of a complex ‘information network’ rather than of discrete, linear systems. Despite the multiplicity of signalling pathways that can be involved, the tumour cells that emerge as the result of appropriate groups of mutations are phenotypically similar in that they share the characteristics discussed in the previous chapter. This suggests that the diverse pathways converge on a ‘central axis’ and in this chapter we’ll look first at the central defenders that do indeed constitute the heart of our protection mechanisms against cancer. We’ll then overlay the major pathways from receptor to nucleus to show how they impact on the central axis and then dissect from that complex map each of the pathways in turn to introduce the key players. The intention is not to show all known detail but to convey the principal features of the pathways with particular emphasis on identified (proto-)oncogenes and tumour suppressors.