This chapter examines cellular cancers, tracing cancer cells from their origins through the evolution to malignancy and concluding with a discussion of strategies for dealing with the threats they represent.

Section 1 - Nasty Novelties

This section begins by establishing the differences between cancers and normal tissues and discussing various types of cancers. Then the idea is developed that cancer cells are regenerating cells which undergo abnormal evolutionary changes, such as excessive proliferation and a failure to differentiate into useful cells. The possible sources of those abnormalities are explored and the most prominent source is identified as genomic changes, which sets the scene for an examination of the kinds of genomic changes that have been found to produce cancerous behaviour in regenerating cells.

Section 2 - Dangerous Possibilities

This section begins with a discussion of various laboratory studies that have uncovered mutations which can make cells behave like cancer cells. Such oncogenic mutations have been found to affect cellular functions ranging from the detection of signals relating to developmental decisions (e.g. whether to divide, differentiate or die), to the passing of signals through cells into the nucleus, to the interpretation of signals by the nuclear machinery and the innermost workings of the cellular command centre itself - for instance some mutations commit cells to dividing no matter what signals are coming from outside. All of these mutations have the potential to free regenerating cells from the influences that normally guide decisions associated with division, differentiation and death, but that does not mean that every possibility will be reflected in the cancer cells that actually appear within bodies - in order to understand their evolution it must be examined directly.

The exploration of real-world cancers begins by examining cases where well-studied oncogenic mutations have been shown to play important roles, such as in familial retinoblastoma. The focus then shifts to an examination of rapidly-evolving cancers like leukemias which require few genomic changes to achieve malignancy, and slowly-evolving cancers where the progression to malignancy involves several genomic changes and possibly physical adaptations as well. The point is made that the evolution of each cancer cell lineage and population is unique with regards to the timing and combination of changes, although certain kinds of changes (e.g. diagnostic chromosome mutations) are associated with particular evolutionary pathways.

The discussion then moves on to consider how cancer cells acquire changes as they evolve, beginning with obvious sources of genomic change such as replication errors (which inevitably accumulate over time) and DNA damage due to mutagens. The effects of cell-stimulatory factors and toxins are also considered, as are potential synergies among the carcinogenic influences that are part of life and/or inherent in the environments we have made for ourselves. Those interactions serve as a lead-in for a discussion of why cancer cells evolve to malignancy.

Section 3 - Malignancy and Momentum

Cancer cells are often said to "progress to malignancy," but their evolution is not progressive in the sense of that it follows preordained routes towards specific goals - which is hardly possible given that most of the critical changes associated with cancer cell evolution are random mutations. There does, however, seem to be a certain relentlessness in the way some cancer cells evolve towards malignancy, and this section examines the influences that can encourage cells to acquire malignant characteristics. The most significant of those influences is natural selection, which encourages cancer cells to participate in struggles to survive and contests to contribute to posterity not as components of larger organizations (i.e. their host bodies), but as organisms living within vast communities that also happen to be organisms. Within that context of existence there are advantages to be gained by cells, lineages and populations that can tap into new resources (e.g. tumours attract blood vessels), reproduce rapidly, spread out to colonize new sites within the body and learn how to evade natural and/or man-made defences, and such changes can actually help and encourage others to develop. Of course many of the traits that are advantageous to cancer cells in their struggles for survival and success also make them increasingly malignant towards their surroundings and their host, but from their perspective that is irrelevant because like all cells they have no way of recognizing the ultimate consequences of their evolution.

This puts the onus for forestalling the malignant evolution of cancer cells upon their hosts, where the main problem is that most of our natural defences against invaders are designed to ignore components of the body itself, which cancer cells still resemble in many respects. It is the differences between cancerous and normal cells that provide the keys to strategies aimed at dealing with cancers.

Section 4 - The Enemy Within

This section considers approaches to dealing with the threats posed by cancers to human health and well-being. It begins with a survey of traditional strategies for identifying and removing cancer cells from the body, and then moves on to consider some of the new approaches that are being developed using the vast amount of information that has been gathered concerning cancer cells and their evolution. For instance some of the new directions in treatment involve activating the immune system against cancer cells, targeting them with smart drugs, using growth factors to trick cancer cells into differentiating or dying, and developing ways of cutting them off from the resources they require for growth using anti-angiogenesis factors.