James DeGregori
James DeGregori is an American cancer biologist, professor of biochemistry and molecular genetics at the University of Colorado Anschutz Medical Campus, known for the theory of adaptive oncogenesis.
Adaptive oncogenesis
The conventional view of cancer risk holds that the somatic mutation burden accumulated with age and over a lifetime is the dominant driver of cancer. DeGregori’s adaptive oncogenesis framework adds a selection-centered correction: whether an oncogenic mutation confers an advantage depends on the state of the tissue it arises in. In young, healthy tissue, most oncogenic mutations are maladaptive — cells carrying them compete poorly against fitter wild-type neighbors. Aging, and other insults that degrade tissue function, change the fitness landscape: the environment becomes one in which previously disadvantaged oncogenic phenotypes can outcompete normal cells.
On this view, aging promotes cancer less by creating mutations than by changing which mutations are selected. The framework reframes cancer prevention as a problem of maintaining tissue environments in which oncogenic cells lose, and it explains observations — such as the weak correlation between lifetime cell divisions, mutation loads and cancer risk across tissues — that mutation-accumulation models struggle with.
His book Adaptive Oncogenesis: A New Understanding of How Cancer Evolves Inside Us (2018) presents the framework for a general audience.
Notes
- Draft stub — maintenance agent to expand with the stem cell competition experiments and the PNAS/Nature papers.