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Published on: December 19, 2019
An evolutionary model for initiation, promotion, and progression in carcinogenesis.
1Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721-0119, USA. vincent@u.arizona.edu
International Journal of Oncology
|March 25, 2008
Summary
This study models human carcinogenesis as an evolutionary process, reconciling empirical observations with genetic changes. The model explains cancer initiation, promotion, and progression through cellular dynamics and microenvironmental adaptations.
Area of Science:
- Evolutionary biology
- Cancer research
- Cellular dynamics
Background:
- Human carcinogenesis is a multistep process involving epithelial cells progressing through premalignant phenotypes to invasive cancer.
- Empirical observations divide carcinogenesis into initiation, promotion, and progression eras.
- Existing models lack reconciliation between tissue-level observations and step-wise genotypic/phenotypic changes.
Purpose of the Study:
- To analyze an evolutionary model of cellular dynamics in carcinogenesis.
- To reconcile empirical observations of carcinogenesis with evolutionary paradigms.
- To provide insights into cellular and microenvironmental dynamics governing cancer development.
Main Methods:
- Analysis of an evolutionary model of cellular dynamics.
- Utilizing an adaptive landscape to illustrate cellular evolutionary potential.
- Simulations based on a dynamic model of tumor growth and morphology.
Main Results:
- Normal epithelial cells possess an adaptive landscape allowing coexistence and mutant invasion.
- Cancer evolution is facilitated by relaxed growth constraints and microenvironmental adaptations.
- Simulations generated three distinct carcinogenesis stages: initiation, promotion, and progression.
Conclusions:
- The dynamic model aligns with empirical stages of carcinogenesis.
- The model offers insights into underlying cellular and microenvironmental dynamics.
- Novel experimental prevention strategies are suggested by the findings.
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