Proceedings of the National Academy of Sciences · 2003 · 245 citations · 15 references
Life SciencesCancer BiologyEvolutionary BiologyCarcinogenesisEvolutionary TheoryNeoplasiaCancer ProgressionCell Population DynamicsEvolutionEvolutionary DynamicsNatural SelectionNeoplastic TransformationCancer-associated Mutational ProcessesEvolutionary Population DynamicsGross Reproductive RateNet Reproductive RateStochastic Evolutionary DynamicsStochastic Processes In BiologyTumor Evolution ModelingTumor Evolutionary Dynamics
Cancer is the consequence of an unwanted evolutionary process. Cells receive mutations that alter their phenotype. Especially dangerous are those mutations that increase the net reproductive rate of cells, thereby leading to neoplasia and later to cancer. The standard models of evolutionary dynamics consider well mixed populations of individuals in symmetric positions. Here we introduce a spatially explicit, asymmetric stochastic process that captures the essential architecture of evolutionary dynamics operating within tissues of multicellular organisms. The "linear process" has the property of cancelling out selective differences among cells yet retaining the protective function of apoptosis. This design can slow down the rate of somatic evolution dramatically and therefore delay the onset of cancer.
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Evolutionary Rate at the Molecular Level
Nature · 1968 · 3.8K citations
Genetic instability in colorectal cancers
Christoph Lengauer, Kenneth W. Kinzler, Bert Vogelstein · Nature · 1997 · 2K citations
Mutation selection and the natural history of cancer
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A Mutator Phenotype in Cancer 1
Lawrence A. Loeb · 2001 · 672 citations