Principles of Tumor Biology

The word “cancer” like the word ”infection,” is a broad term. It is used to describe a pathologic process involving uncontrolled cell growth and proliferation. There are about 200 different cancers with different behaviors and outcomes. Cancer, like an infection, can be rapidly devastating and fatal, or curable and minor depending on the tumor type involved.
It can be described as a disease of the genome, with a cancer arising from the accumulation of several genetic mutations that act in a way that eliminates normal regulation of cell proliferation and impacts on genetic integrity. This in turn allows the proto-cancer cells to acquire other mutations that are needed for a cancer to develop and survive within the body.
The initial mutations can either be inherited or acquired as part of the inherent error rate of accurately replicating each of the approximately 2.7 billion base pairs in a horse’s DNA during normal cell division. They can be driven by other mutagens (environmental or infectious) which directly or indirectly increase the rates of repair of DNA within the target tissue, and thus increase the risk of errors.
When a mutation arises the impact it has depends on the effect it has on the protein coded for. They can be irrelevant—being either silent, meaning that the cell continues to function normally, or they can be fatal to the cell, so the cell fails to replicate and pass on the mutation. However, some mutations provide a step along the pathway to that cell’s progeny becoming neoplastic. The genes that are involved in maintaining DNA integrity from cell cycle to cell cycle are particularly important. Once these gatekeepers cease to function properly each cell’s daughter cells are inherently genetically unstable, and will express more genetic mutations, some of which will confer a survival advantage to that particular cell line and ultimately give rise to the initial clonal expansion of 1 cell that categorizes the development of a tumor.
There are an estimated 22,000 protein coding genes in the horse that can be randomly switched “on” or “off” as part of this genetic instability to confer that survival advantage. The easiest way to consider this in more detail is to look at the “hallmarks of cancer.”