In order for a cell to become cancerous, it must overcome a great number of biological safeguards. One of the hallmarks of cancer cells is unrestricted cell growth. Cell growth is highly regulated through different growth control checkpoints. These checkpoints serve as gatekeepers that only allow healthy cells to grow. Early in cancer development cancer cells become unresponsive to these checkpoints facilitating unrestrictive cell growth. In addition to avoidance of cell control checkpoints, cancer cell must also acquire the ability to sustain their own growth, avoid cell death signals, overcome environmental challenges such as nutrient deprivation, lack of oxygen and evade the immune response. Driving this multi-step processes is evolution through natural selection.
Evolution through natural selection requires at least two components: first is the generation of “genetic diversity” and the second is the selection of those genetic variants that may confer an evolutionary advantage.
In cancer cells, genetic diversity arises through the accumulation of mutations. Mutations are changes in the genetic code that may or may not alter the function of a protein. Most mutations are either deleterious or neutral. However, in some rare cases a mutation may give cells an advantage over other cells, allowing the mutation to overtake the population. This process is generally referred to as selection. Selection of a particular mutation is contingent upon the environmental context in which the mutation is present. Some mutations can be advantageous in a particular environment, whereas in other environments they can be disadvantageous.
It is thought that early in cancer development cells acquire what is called a “mutator phenotype”. This means that cancer cells develop the capacity to increase the number of mutations they acquired per generation. This directly increases the pool of new traits that can be selected enabling cancer formation, progression and metastasis. Intrinsically cancer is an evolutionary problem. Cancer treatments have to constantly be ahead of cancer’s ability to develop resistance to chemotherapeutic through natural evolutionary processes. This accentuates the necessity for better understanding of these processes and the concomitant development of therapies that avoid such evolutionary traps.
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