Putting tumours in context

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Abstract
Cell–cell and cell–ECM signalling contributes to epithelial structure and function and creates innate anticancer mechanisms that suppress tumorigenicity. The development of carcinomas involves progressive changes in the malignant cells, in the associated stromal compartment and in the extracellular milieu. These changes lead to an ever-changing functional disorder, in which the aberrant context affects cell–cell and tissue–tissue interactions. The tumour context includes both normal cells and tissues that aid in the progression of the tumour. The tumour, in turn, modifies the behaviour of the 'normal' component of the tumour. The tumour context is both self-sustaining and progressive, but can be modified through alterations in signalling that affect the structure and function of tumour cells; malignant epithelial cells can be reverted to a normal phenotype despite the aberrant genotype. To achieve reversion of a tumour tissue, both the tumour cells and their microenvironment need to be modified. As such, a combination of signalling inhibitors and agents that 'deactivate' the reactive stroma is required. Haematologic tumours develop (and can now be treated) according to many of these same principles. A better understanding of the mechanisms by which the tumour context creates the functional disorder within the tumour organ is a means of potentiating existing anticancer therapies and of developing a new generation of even more successful therapies.